Saracens have recalled several players from Six Nations duty and rest periods during the LV= Cup for Saturday's clash with Quins at Wembley.
With the game set to draw a world record crowd for club rugby union fixture, Saracens fly-half Charlie Hodgson will play his 100th game for the club.
Hodgson is named alongside experienced scrum-half Neil de Kock, who is set to make his eleventh appearance for Saracens at Wembley Stadium.
In the midfield, Chris Wyles comes into the side at inside centre to partner Argentine Marcelo Bosch.
Fresh from his brace of tries in Saracens' 23-20 LV= Cup final victory against the Exeter Chiefs, prolific wing David Strettle takes his place on the left wing and is joined by fellow try poacher Chris Ashton and England full-back, Alex Goode, in the Saracens back three.
Up front, Mako Vunipola takes his place in the front-row to join Jamie George (hooker) and Juan Figallo (tighthead prop). Elsewhere in the engine room, England lock forward George Kruis returns to the starting line-up alongside skipper Alistair Hargreaves in the second-row.
England back-row star Billy Vunipola is named at eight, and he is joined by Jackson Wray and Jacques Burger in Saracens' loose forward trio.
Meanwhile, Chris Robshaw, Nick Easter and captain Joe Marler start for Harlequins after returning from international duty during the Six Nations.
Full-back Mike Brown also returned from England following the match against France and is suffering from symptoms of concussion. Ross Chisholm starts at full-back as Brown is expected to return for the Gloucester match.
There are just four changes to the starting team that played London Irish; alongside the returning internationals, Ugo Monye and Kyle Sinckler are named.
In the second-row, George Robson will make his 200th appearance for the club.
Form: While Harlequins' only victory in their last 13 fixtures in all competitions against Saracens came at Wembley three years ago, Mark McCall's side have lost just once in their last eight games in all tournaments. Saracens have a mixed record at Wembley with three wins, one draw and three losses in their last seven fixtures but will be driven to remain in contention for a home Aviva Premiership Rugby semi-final this season.
Saracens: 15 Alex Goode, 14 Chris Ashton, 13 Marcelo Bosch, 12 Chris Wyles, 11 David Strettle, 10 Charlie Hodgson, 9 Neil de Kock, 8 Billy Vunipola, 7 Jacques Burger, 6 Jackson Wray, 5 Alistair Hargreaves (c), 4 George Kruis, 3 Juan Figallo, 2 Jamie George, 1 Mako Vunipola.
Replacements: 16 Scott Spurling, 17 Rhys Gill, 18 Biyi Alo, 19 Maro Itoje, 20 Kelly Brown, 21 Richard Wigglesworth, 22 Nick Tompkins, 23 Catalin Fercu.
Harlequins: 15 Ross Chisholm, 14 Marland Yarde, 13 Matt Hopper, 12 Harry Sloan, 11 Ugo Monye, 10 Nick Evans, 9 Danny Care, 8 Nick Easter, 7 Chris Robshaw, 6 Jack Clifford, 5 George Robson, 4 Charlie Matthews, 3 Kyle Sinckler, 2 Dave Ward, 1 Joe Marler (c).
Replacements: 16 Rob Buchanan, 17 Mark Lambert, 18 Matt Shields, 19 Netani Talei, 20 Luke Wallace, 21 Karl Dickson, 22 Ben Botica, 23 Charlie Walker.
Date: Saturday, March 28
Venue: Wembley Stadium, London
Referee: Wayne Barnes
Assistant Referees: Paul Dix, Roger Bayliff
TMO: Geoff Warren