The King George VI Chase winner is among 15 contenders after last year’s runner-up Minella Rocco, Double Shuffle and Shantou Flyer were withdrawn.
Victory would make Henderson the first trainer to win the Champion Hurdle, Champion Chase and Gold Cup at one Cheltenham Festival meeting.
Native River and Our Duke are among the favourites for the 15:30 GMT race.
A sell-out crowd of 70,000 is expected at the Gloucestershire track, where the going is described as soft, heavy in places.
Minella Rocco was taken out by trainer Jonjo O’Neill on Friday morning because of the going, but last year’s third-placed horse Native River runs for Colin Tizzard.
The 2017 champion Sizing John misses out through injury for trainer Jessica Harrington, but she will be represented by Irish Grand National winner Our Duke.
Edwulf, who nearly died at the meeting last year, runs after a remarkable recovery which saw him win the Irish Gold Cup last month.
Lizzie Kelly, victorious on Coo Star Sivola earlier in the week, partners Tea For Two as she bids to become the first female jockey to win the Cheltenham Gold Cup.
- Cheltenham Gold Cup: All the runners and riders
- Record for Mullins as Irish dominate at Cheltenham Festival
- Listen: Cheltenham podcast – ‘It’s all about the Irish’
- All the fun of the Festival – Relive day three at Cheltenham
Can Henderson make history?
Might Bite secured the RSA Chase at the Festival last year despite swerving dramatically in the final stages.
Ridden by Nico de Boinville, he went on to win the King George at Kempton on Boxing Day from Double Shuffle and Tea For Two.
Henderson saddled Buveur D’Air to win a second Champion Hurdle on Tuesday and won the Queen Mother Champion Chase with Altior 24 hours later.
“It’s funny how champions come around in the same breath, but I feel they help each other – if you have good horses, they make good horses,” said the 67-year-old.
Analysis
Cornelius Lysaght, BBC racing correspondent
It’s an open Gold Cup, and though some will say it’s more about quantity than quality we do have Might Bite, the King George winner looking to scale the second of steeplechasing’s two major peaks.
If Might Bite was guaranteed to run in a straight line, his odds would be miles shorter; I’ve no real doubts his stamina will last out the distance.
Of the admittedly fairly long list of alternatives, Willie Mullins’ four – probably headed by Killultagh Vic who’s a class act – attempt to give the prolific stable success after no fewer than six seconds, and Ireland is rampant here this week, while no-one must forget Definitly Red, who’ll revel in the going and has good recent Cheltenham form.
Friday’s schedule
(All times GMT, distances in miles and furlongs)
13:30: JCB Triumph Hurdle 2m 1f
14:10: Randox Health County Handicap Hurdle 2m 1f
14:50: Albert Bartlett Novices’ Hurdle 3m
15:30: Cheltenham Gold Cup Chase 3m 2½f
16:10: St. James’s Place Foxhunter Steeple Chase Challenge Cup 3m 2½f
16:50: Martin Pipe Conditional Jockeys’ Handicap Hurdle 2m 4½f
17:30: Johnny Henderson Grand Annual Handicap Chase 2m 1½f
- Racecards and results
What makes the race special?
The Gold Cup is a test for the top steeplechasers who must negotiate 22 fences over three miles and two furlongs.
Jockey Andrew Thornton, who won on Cool Dawn in 1998: “It’s a privilege to take part. From a jockey’s point of view it’s like the FA Cup and Champions League rolled into one.
“It means everything to win it. You’re introduced as the Cheltenham Gold Cup-winning jockey and that feels great.”
Commentator John Hunt: “The atmosphere is different to the other races. There’s an added element of tension with the Gold Cup. That’s the one race people want to win and will remember. Calling home the victor is always special.”
Tips from the 5 live team
There may be 15 runners, but our pundits are agreed on the winner.
Thornton: “Our Duke in The Gold Cup stands out to me. He’ll relish the soft ground. He’s a young horse who’s still improving. Last time out he beat Presenting Percy, who won the RSA Chase here on Wednesday.”
Reporter Gina Harding: “Treatment for some injury problems has clearly paid off and Our Duke’s prep run for this race was further proof of his renewed wellbeing. In a wide-open renewal of the race he looks to hold an excellent chance.”
Hunt: “Our Duke made astonishing progress last year. He’s a guaranteed stayer who will love the ground. What more could you want? No wonder we have all gone for him.”
Kelly eyes landmark
After previous successes for amateur riders, Kelly was the first female professional jockey to win at the Festival when triumphing aboard Coo Star Sivola on Tuesday.
The 24-year-old will be hoping to get further after being unseated at the second fence by Tea For Two, trained by her stepfather Nick Williams, 12 months ago.
She was the first female rider to compete in the race for 33 years, but says women compete on an equal footing.
“I work in a wonderful environment with gentlemen, jockeys who look out for each other. They’re concerned if you have a fall, and pleased if you win. It’s a nice gang to be a part of,” she said.
“I’m happier with Tea For Two going into the race this year. I can’t wait to get out there and give it another bash and perhaps don’t feel as much pressure.”
Edwulf – ‘The Miracle Horse’
It has been quite a year for Edwulf, trained by Joseph O’Brien, after he fell at the final fence in the 2017 National Hunt Chase and the Cheltenham racecourse veterinary team worked for more than an hour to save him.
“I think he was blind for a time – it’s quite unbelievable that he could come back, and it’s a testament to the horse and his attitude,” said O’Brien, the 24-year-old son of record-breaking champion trainer Aidan.
After a series of tests, Joseph and owner JP McManus were assured the occurrence was no more likely to happen again to the nine-year-old as it might to any other horse.
A former Classic-winning jockey, O’Brien is seeking another big success after landing the Melbourne Cup in November with Rekindling.
- Read more on the Edwulf story here
Willie Mullins passed Henderson as the Festival’s all-time leading trainer when he clocked up his 61st victory on Thursday.
And Mullins, who has saddled the runner-up six times, fields four runners as he seeks a first Gold Cup win.
Paul Townend rides Killultagh Vic in the absence of the injured Ruby Walsh while Willie’s son Patrick is aboard Djakadam, who was second in 2015 and 2016. Total Recall and Bachasson are other Mullins challengers.
Shantou Flyer, second to Coo Star Sivola earlier in the week, was withdrawn from the race on Friday morning.
The field is completed by American, Anibale Fly, Definitly Red, Outlander, Road To Respect and Saphir Du Rheu.
Thunder at Cheltenham?
By BBC 5 live weather forecaster Simon King
Friday will get off to a largely dry start with some sunny spells. However, into the afternoon and racing, we’re expecting some heavy, possibly even thundery showers to develop.
Whether these showers hit Cheltenham racecourse itself is difficult to pin down but there is a risk of a downpour giving 5-10mm of rain. It will feel cooler, with a high of 10C.
source:-bbc.c