Jamie Roberts will make his Premiership debut for Harlequins against Gloucester at Twickenham on Sunday.
Returning to the Premiership following back to back victories over Calvisano in the Challenge Cup, there are 12 changes to the matchday squad.
Mike Brown, George Lowe, Tim Visser, Nick Evans and captain Danny Care return to the backline.
In the forwards, Joe Marler, Will Collier, James Horwill, Chris Robshaw and Nick Easter are named, with Dave Ward starting at hooker.
Care, Brown and Easter have played in every Big Game to date.
Meanwhile, Greig Laidlaw will skipper Gloucester as they resume their Premiership campaign.
Laidlaw and Billy Twelvetrees have both captained the side this season, but the Scottish scrum-half will wear the arm band for the Quins game.
It's a strong line-up which features 12 internationals in the starting XV. Laidlaw will partner James Hook at half-back and Twelvetrees will line up alongside Bill Meakes in the midfield. The back three will feature Rob Cook, Jonny May and Charlie Sharples.
The front row will consist once again of Paddy McAllister, Richard Hibbard and John Afoa, while Jeremy Thrush and Mariano Galarza team up for the first time in the second row. The back row will comprise Sione Kalamafoni, Matt Kvesic and Ben Morgan.
Director of rugby David Humphreys is well aware of the challenge posed by Harlequins, led by his good friend Conor O'Shea.
"They've been very successful over the last number of years and have been one of the form teams in the competition this year. They're certainly going into this week's game as strong favourites.
"But that's the challenge for us. They're a team we want to compete against and we believe, with the squad and the players we have, we can do so. But we have to go up to Twickenham and back up that belief with a really big performance.”
Form: This is the eighth "Big Game" at Twickenham where Harlequins previous record is an even won three, drawn one, lost three. Harlequins have lost just one of their last eight fixtures in all competitions: 25-26 at Exeter in Round 5 of Premiership. Quins only defeat at home in any tournament since February was 26-27 to Bath in Premiership in May. Harlequins loss to Northampton in last season's "Big Game" ended a six game winning run in all tournaments at Twickenham Stadium. Gloucester have lost just one of their last six encounters in all competitions: 3-15 at Northampton in Premiership Rugby on November 27. The Cherry & Whites have lost on their last five visits to Twickenham Stadium since beating Northampton there in the final of the Powergen Cup in April 2003. Harlequins recorded a Premiership Rugby double over Gloucester last season something that they had not achieved since 1998/99. The two sides have met twice before at Twickenham Stadium in major competitions, with Gloucester winning 12-6 in the semi-final of the John Player Cup in April 1978 and a 9-all draw in a Courage League Division 1 encounter in November 1987.
Harlequins: 15 Mike Brown, 14 Marland Yarde, 13 George Lowe, 12 Jamie Roberts, 11 Tim Visser, 10 Nick Evans, 9 Danny Care (c), 8 Nick Easter, 7 Jack Clifford, 6 Chris Robshaw, 5 Charlie Matthews, 4 James Horwill, 3 Will Collier, 2 Dave Ward, 1 Joe Marler
Replacements: 16 Rob Buchanan, 17 Mark Lambert, 18 Kyle Sinckler, 19 George Merrick, 20 Luke Wallace, 21 Karl Dickson, 22 Ben Botica, 23 Ross Chisholm
Gloucester: 15 Rob Cook, 14 Charlie Sharples, 13 Billy Meakes, 12 Billy Twelvetrees, 11 Jonny May, 10 James Hook, 9 Greig Laidlaw (c), 8 Ben Morgan, 7 Matt Kvesic, 6 Sione Kalamafoni, 5 Mariano Galarza, 4 Jeremy Thrush, 3 John Afoa, 2 Richard Hibbard, 1 Paddy McAllister
Replacements: 16 Darren Dawidiuk, 17 Dan Murphy, 18 Paul Doran-Jones, 19 Tom Savage, 20 Jacob Rowan, 21 Willi Heinz, 22 Billy Burns, 23 Henry Trinder
Date: Sunday, December 27
Kick-off: 16:30 GMT
Referee: Wayne Barnes
Assistant Referees: Gregory Garner, Wayne Falla
TMO: Graham Hughes