Adam Thompstone comes into the back three to join Delon Armitage and Topsy Ojo. Shontayne Hape will start in the centre with Jonathan Spratt, while Faan Rautenbach returns to the front row and David Sisi will start at openside flanker.
London Irish head coach Toby Booth knows his charges cannot afford to slip up against the Welsh region.
"Cardiff is a must win match if we are to remain in the Heineken Cup," he said.
"We're still in this tournament and fighting for our place. It will be another tough encounter but we will be ready for the challenge," added Booth.
Meanwhile, Gavin Henson will start at inside centre for the Blues as they look to repeat the win they notched up against the Exiles in November.
There are three changes in the backs, with Henson having his first run out at inside centre for the Blues, having impressed with his displays at full back.
The Blues have also included two new wingers with Alex Cuthbert returning having recovered from a groin injury and Chris Czekaj from a hamstring strain.
There are a further four new faces in the pack with T Rhys Thomas returning from a neck injury and Fau Filise from a shoulder problem, both starting in the front row.
The visitors have an all new second row with Bradley Davies and captain Paul Tito both starting. Michael Paterson moves to blindside in place of Maama Molitika who moves down to the bench.
London irish:15 Delon Armitage, 14 Topsy Ojo, 13 Jonathan Spratt, 12 Shontayne Hape, 11 Adam Thompstone, 10 Adrian Jarvis, 9 Darren Allinson, 8 Alex Gray, 7 David Sisi, 6 Bryn Evans, 5 Matt Garvey, 4 Nick Kennedy, 3 Faan Rautenbach, 2 David Paice, 1 Clarke Dermody (c).
Replacements: 16 James Buckland, 17 Alex Corbisiero, 18 Paulica Ion, 19 Bob Casey, 20 James Sandford, 21 Tom Homer, 22 Steven Shingler, 23 Paul Hodgson.
Cardiff Blues:15 Leigh Halfpenny, 14 Alex Cuthbert, 13 Casey Laulala, 12 Gavin Henson, 11 Chris Czekaj, 10 Dan Parks, 9 Lloyd Williams, 8 Xavier Rush, 7 Sam Warburton, 6 Michael Paterson, 5 Paul Tito (c), 4 Bradley Davies, 3 Taufa'ao Filise, 2 T Rhys Thomas, 1 Gethin Jenkins.
Replacements: 16 Ryan Tyrell, 17 John Yapp, 18 Scott Andrews, 19 Maama Molitika, 20 Josh Navidi, 21 Richie Rees, 22 Ceri Sweeney, 23 Richard Mustoe.
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