"This is a pretty intense period of rugby, especially with two big, physical games against Perpignan in the last couple of weeks, so it is important that we look after the players and manage the squad," said Tigers director of rugby Richard Cockerill. "We also have the England rest periods and a few injuries to deal with, but we've got a good squad and I'm looking for a big performance in front of a full house at Welford Road.
"We had a very good win away to London Irish in our last league game and we need to maintain our momentum and keep hold of that place in the top four of the table."
Manu Tuilagi starts at centre, while James Grindal and Jeremy Staunton form the half-back partnership. Rob Hawkins and Ed Slater come into the forward pack, with Steve Mafi continuing in the back row alongside Craig Newby and Thomas Waldrom.
Ben Youngs, Dan Cole and George Chuter are rested in accordance with the terms of the England EPS agreement, while Toby Flood and Jordan Crane are ruled out this week due to injury.
Prop Faan Rautenbach will make his 100th appearance for London Irish later today when they meet Harlequins for the first time this season in the Premiership away at Twickenham.
The powerful South African joined London Irish from Western Province in September 2005 and has been a key member of the forward pack ever since. With 14 caps for the Springboks, Faan is an experienced, international prop whose technique and strength is well respected by his peers.
Other changes see Topsy Ojo return to the starting line up.
London Irish Head Coach, Toby Booth said: "We're looking forward to meeting Harlequins. As local rivals our games always deliver exciting, competitive performances."