Harlequins will likely need a victory to stand any chance of leapfrogging Gloucester or Sale to claim a Champions Cup spot, but Northampton, who have already secured top spot, stands in their way.
Quins will finish eighth if they better the result of Gloucester, who take on bottom side Newcastle Red Bulls. There is also the possibility Harlequins could finish above seventh-placed Sale if they pick up a bonus point win and Sharks lose by more than seven points to Bristol.
Jason Gilmore makes five changes from the Quins side that lost 26-12 to London rivals Saracens, with Stephan Lewies returning at second row for his last game in place of Elliot Williams.
Cassius Cleaves comes in on the left wing in the only change to the backline, replacing Sean Kerr, with Cadan Murley shifted to outside centre.
Tighthead prop Ollie Streeter replaces Pedro Delgado, who drops to the bench, and lock Jonny Green replaces Zach Carr, while Will Evans is in at flanker for Chandler Cunningham-South.
Jamie Benson starts at full-back for his final game for the club, and Tom Lawday, who is leaving after seven years at The Stoop, is among the replacements.
Northampton Saints full-back George Furbank will not feature against the club he is set to join next season as Phil Dowson names just two players from the XV that started the narrow victory against Gloucester last Saturday.
Tom Litchfield remains at outside centre, and flanker Tom Pearson switches from blindside to openside after Northampton guaranteed a home fixture in the post-season shake-up last week.
Fraser Dingwall partners Litchfield in the backs as captain while Western Force-bound James Ramm starts on the wing and hooker Curtis Langdon returns to the side.
There is no place in the 23 for England quartet Fin Smith, Tommy Freeman, Alex Coles and Henry Pollock with the Prem semi-finals on the horizon next weekend.
Harlequins: Benson; Anderson, Murley, Bradley, Cleaves; Smith, Porter; Hobson, Riley, Streeter; Green, Lewies, Kenningham, W Evans, Dombrandt (capt).
Replacements: Staples, Wenger, Delgado, Treadwell, Petti, Lawday, Townsend, Bellamy.
Northampton: Pater; Martin, Litchfield, Dingwall (capt), Ramm; Belleau, Weimann; Fischetti, Langdon, Kundiona; Lockett, Van der Mescht, Kemeny, Pearson, Graham.
Replacements: Wright, West, Tonga’uiha, Munga, Chick, James, Thame, Hendy.