Victory would secure top spot in Pool Two and give the Tigers a place in the semi-finals of the cup competition for the first time since 2008.
Horacio Agulla, Anthony Allen and Jeremy Staunton return to the Tigers back division, while there are recalls for Marcos Ayerza, George Chuter, Julian White and Steve Mafi amongst the forwards, as well as Thomas Waldrom who is included after he was released from England training this week.
Ben Woods, who led Leicester to victory at Harlequins in round three, will captain the team on home soil for the first time.
Craig Newby is included in the senior squad for the first time since leading the team in last season's Aviva Premiership Final following his recovery from a knee injury, and fly-half Toby Flood is back in the matchday squad after a hamstring injury.
Director of rugby Richard Cockerill, who saw a young side win at Harlequins in round three last weekend, is without four England players on international duty and Martin Castrogiovanni who is away with Italy.
Meanwhile, Billy Twelvetrees and Ed Slater are with the England Saxons and George Ford is captaining the England U20s.
For their part, Newcastle Falcons have made three changes to their starting XV as new director of rugby Gary Gold targets back-to-back victories.
Gold, who guided his side to a comprehensive 37-7 triumph over Sale Sharks last weekend, has thrown Jonny Golding into the mix after five months out with persistent Achilles problems.
Golding starts in the front-row after playing the final 15 minutes of last Sunday's thumping home success, but fellow props Dan Frazier and Grant Shiells miss out with respective back problems.
Greg Goosen returns at full-back after three weeks out with a cyst in his calf, while points machine Jimmy Gopperth moves back to his favoured fly-half berth.
Richard Mayhew rounds off the changes with the English qualified Kiwi getting the nod in the back-row. Samoan Jamie Helleur has a place on the bench after being sidelined with a finger injury.
Sitting on 10 points, four points behind the Scarlets in their pool, Newcastle still have a mathematical chance of progressing through to the semi-finals.
Leicester: 15 Niall Morris, 14 Horacio Agulla, 13 Matt Smith, 12 Anthony Allen, 11 Scott Hamilton, 10 Jeremy Staunton, 9 Sam Harrison, 8 Thomas Waldrom, 7 Ben Woods (c), 6 Steve Mafi, 5 Graham Kitchener, 4 George Skivington, 3 Julian White, 2 George Chuter, 1 Marcos Ayerza.
Replacements: 16 Rob Hawkins, 17 Logoviii Mulipola, 18 Ryan Bower, 19 Craig Newby, 20 Julian Salvi, 21 James Grindal, 22 Toby Flood, 23 Andy Forsyth.
Newcastle: 15 Greg Goosen, 14 Ryan Shortland, 13 Corne Uys, 12 James Fitzpatrick, 11 Suka Hufanga, 10 Jimmy Gopperth, 9 Chris Pilgrim, 8 Mark Wilson, 7 Richard Mayhew, 6 Ally Hogg, 5 Tim Swinson, 4 Adriaan Fondse, 3 James Hall, 2 Rob Vickers, 1 Jonny Golding.
Replacements: 16 Joe Graham, 17 Darren Fearn, 18 Ashley Wells, 19 Richard Boyle, 20 Taiasina Tu'ifua, 21 Will Chudley, 22 Jamie Helleur, 23 Joel Hodgson.
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