Alex Coles once again skippers a young Saints side, but the 22-year-old switches from flanker to lock for the showdown with Quins, joining Alex Moon in the engine room.
That paves the way for Senior Academy players Ollie Newman and Geordie Irvine to make their first starts for Saints in the back row, with Karl Wilkins switching from No.8 to flanker.
Tighthead Conor Carey is another in line for a maiden Saints start, with hooker Mike Haywood also coming into the front row and loosehead Emmanuel Iyogun rounding off the pack.
Two changes to Saints’ back-line see Tom Collins come onto the wing, and scrum-half Connor Tupai make his first start of the season.
That means James Grayson continues at fly-half, with the centre partnership of Tom Litchfield and Rory Hutchinson unchanged.
Wing Josh Gillespie and full-back George Hendy complete the line-up in the back three after the duo both got on the scoresheet last time out.
Amongst the replacements, JJ Tonks returns from injury to feature in a matchday 23 for the first time this season, while wing Courtnall Skosan will be hoping to build on an impressive start to his Saints career, having scored five tries in three appearances so far.
Meanwhile, Harlequins have made four changes to the team that lost to Saracens last weekend.
Tongan international Viliami Taulani will make his debut, having signed during the summer.
Also stepping into the starting 15 this week are Harlequins Academy pair George Hammond and Oscar Beard, with Scott Steele taking up the scrum-half berth.
Hammond pairs with fellow Academy lock Hugh Tizard in the engine room in place of club captain Stephan Lewies, while Beard replaces Ross Chisholm on the wing.
In Lewies' absence, No.8 Archie White takes up the captaincy after a standout showing against Saracens.
Tighthead prop Will Hobson will look to make his senior debut from the bench, with the Academy front-rower replacing Will Collier in the 18 jersey.
Also looking to make his debut this weekend will be former NFL man Christian Scotland-Williamson, who is set for his first game of rugby since 2017.
Harlequins: David; Beard, Jones, Anyanwu, Morris; Benson, Steele, Garcia Botta, Musk, Trenier; Tizard, Hammond; Taulani, Wallace, White (c).
Replacements: Head, Osborne, Hobson, Scotland-Williamson, Alikhan, Stafford, Hyde, Green.
Saints: Hendy; Gillespie, Litchfield, Hutchinson, Collins; J Grayson, Tupai; Iyogun, Haywood, Carey; Moon, Coles (c); Wilkins, Newman, Irvine.
Replacements: Fish, Auterac, Garside, Lockett, Tonks, James, E Grayson, Skosan.