Irish are second from bottom in the Aviva Premiership table with two wins from 12 while the Tigers have won on three of their last four trips to Reading.
Geordan Murphy, Toby Flood, Graham Kitchener and Jordan Crane all return for Leicester.
Club captain Murphy will make his 200th Premiership appearance as he is included in the starting line-up for the first time since the win over Northampton Saints in early November.
He becomes the 19th player to reach that top-flight landmark, with club colleague George Chuter holding the all-time record with 258 appearances.
Fly-half Flood has recovered from a toe injury and makes his first club appearance since the end of October.
Kitchener comes into the second row for Tigers, and Crane takes the number eight shirt with Thomas Waldrom ruled out by a calf injury picked up in last Saturday's Heineken Cup win over Treviso in Italy.
Leicester Tigers scrum-half Ben Youngs said: "We have come out on top of some close games down there in recent years and we have to make sure that doesn't change.
"They have some good open-field runners and we will have to improve from last week against a team that is better than their position in the table."
Marland Yarde has recovered from injury and will start for Irish while Ian Humphreys starts at fly half and Jebb Sinclair joins Declan Danaher and Chris Hala'ufia in the back row.
London Irish director of rugby Brian Smith said: "It will be great to be playing back at the Madejski in front of our home crow.
"Leicester has been the benchmark team in the Aviva Premiership for a long time now and they'll give us a thorough examination. In saying that we don't fear any team in this league and the boys are itching to play the Tigers."
London Irish: 15 Tom Homer, 14 Topsy Ojo, 13 Jonathan Joseph, 12 Sailosi Tagicakibau, 11 Marland Yarde, 10 Ian Humphreys, 9 Darren Allinson, 1 Max Lahiff, 2 David Paice, 3 Halani Aulika, 4 Bryn Evans, 5 Matt Garvey, 6 Declan Danaher (c), 7 Jebb Sinclair, 8 Chris Hala'ufia.
Replacements: 16 Scott Lawson, 17 Jerry Yanuyanutawa, 18 Leo Halavatau, 19 Kieran Low, 20 Jamie Gibson, 21 Guy Armitage, 22 Shane Geraghty, 23 Jack Moates.
Leicester: 15 Geordan Murphy, 14 Niall Morris, 13 Manusamoa Tuilagi, 12 Anthony Allen, 11 Adam Thompstone, 10 Toby Flood, 9 Ben Youngs, 8 Jordan Crane, 7 Julian Salvi, 6 Brett Deacon, 5 Graham Kitchener, 4 Louis Deacon (c), 3 Dan Cole, 2 Tom Youngs, 1 Marcos Ayerza.
Replacements: 16 Rob Hawkins, 17 Logovi'i Mulipola, 18 Fraser Balmain, 19 Ed Slater, 20 Geoff Parling, 21 Sam Harrison, 22 George Ford, 23 Matt Smith.
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