Lyle, who joined the Tigers after moving from Bath, will start at No.8, while lock Brett Deacon and and inside centre Daryl Gibson will also make their first appearance for the side.
England discards Tim Stimpson, Ollie Smith and Graham Rowntree have all been included in a solid starting XV, while Samoan international Henry Tuilagi and Austin Healey, who was also considered surplus to England coach Clive Woodward's needs, have been named on the bench.
Hooker James Buckland, Ireland fullback Geordan Murphy, Tuilagi's brother Freddie and Luke Myring have all been ruled out through injury.
Leicester Tigers: 15 Tim Stimpson, 14 Ollie Smith, 13 Leon Lloyd, 12 Daryl Gibson, 11 John Holtby, 10 Sam Vesty, 9 Harry Ellis, 8 Dan Lyle, 7 Josh Kronfeld (captain), 6 Will Johnson, 5 Brett Deacon, 4 Louis Deacon, 3 Ricky Nebbett, 2 George Chuter, 1 Graham Rowntree.Replacements: 16 Stuart Friswell, 17 Darren Morris, 18 James Hamilton, 19 Adam Balding, 20 Henry Tuilagi, 21 Austin Healey, 22 Steve Booth.
Kick-off: 15.00 BST (14.00 GMT)