It will be the first home league assignment for Conor O'Shea's men since beating Newcastle at the end of November last year.
Ross Chisholm retains his place at full-back from last weekend's high-scoring defeat at Cardiff Blues, alongside Sam Smith and the returning Tom Williams who line up on the wings.
Hopper returns from Saxons duty to partner Tom Casson in the centre, outside half-back pairing Nick Evans and Danny Care.
Mark Lambert, Joe Gray and James Johnston all return to provide the foundation of the scrum. Olly Kohn again partners George Robson in the second row, with Robson taking over the captaincy from Chris Robshaw who will lead England in Rome.
Tom Guest, Luke Wallace and Nick Easter provide the back row, with the likes of Tomas Vallejos, Will Skinner, Rory Clegg and George Lowe providing back-up from the bench.
The Exiles have made five changes from the side that beat Gloucester last weekend for the trip across the capital.
Topsy Ojo is back on the wing with Jonathan Joseph partnering Shontayne Hape in the centres.
Up front, David Paice and Faan Rautenbach are installed in the front row with Kieran Roche taking his place in the back three alongside Richard Thorpe and Matt Garvey.
"It is important that we continue the momentum we gained from last weekend and play with the attacking intent we have shown in recent weeks," stated London Irish head coach Toby Booth.
"Points are crucial at this time of the season as we continue to push for a play-off position. The players have prepared well this week despite the weather and are ready for the contest."
Harlequins: 15 Ross Chisholm, 14 Tom Williams, 13 Matt Hopper, 12 Tom Casson, 11 Sam Smith, 10 Nick Evans, 9 Danny Care, 8 Nick Easter, 7 Luke Wallace, 6 Tom Guest, 5 George Robson (c), 4 Olly Kohn, 3 James Johnston, 2 Joe Gray, 1 Mark LambertReplacements: 16 Chris Brooker, 17 Aston Croall, 18 Tim Fairbrother, 19 Tomas Vallejos, 20 Will Skinner, 21 Karl Dickson, 22 Rory Clegg, 23 George Lowe.
London Irish: 15 Tom Homer, 14 Topsy Ojo, 13 Jonathan Joseph, 12 Shontayne Hape, 11 Sailosi Tagicakibau, 10 Dan Bowden, 9 Darren Allinson, 1 Clarke Dermody (capt), 2 David Paice, 3 Faan Rautenbach, 4 Nick Kennedy, 5 Bryn Evans, 6 Matt Garvey, 7 Kieran Roche, 8 Richard ThorpeReplacements: 16 Brian Blaney, 17 Max Lahiff, 18 Paulica Ion, 19 Ed Siggery, 20 Marland Yarde, 21 Delon Armitage, 22 Adrian Jarvis, 23 Ross Samson.
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