The France international goalkeeper is given his first start for the club since joining on transfer deadline day against the Serie A visitors at White Hart Lane
His current No.1, Brad Friedel, is given a rest as Carlo Cudicini comes in on the bench.
Jermain Defoe is set to continue his run of good form up front with support from Mousa Dembele and Clint Dempsey as Emmanuel Adebayor has been ruled out.
Kyle Naughton continues to deputise at left-back for Benoit Assou-Ekotto, who is out with a knee injury, whilst Scott Parker misses out as this game has come just too quickly for him on his return from an achilles injury.
Germany international Miroslav Klose leads the line for Lazio as they play Tottenham for the first time in Europe.
Tottenham starting XI: Lloris; Walker, Vertonghen, Caulker, Naughton; Sandro, Dembele, Dempsey, Bale, Lennon; Defoe
Substitutes: Cudicini, Dawson, Gallas, Huddlestone, Mason, Townsend, Sigurdsson
Lazio starting XI: Marchetti; Lulic, Andre Dias, Biava, Cavanda; Ledesma; Onazi, Gonzalez, Hernanes, Mauri; Klose.
Substitutes: Bizzarri, Ciani, Scaloni, Ederson, Zarate, Kozak, Floccari.