Lloris replaces veteran Brad Friedel, who is on the bench with his fellow American countryman Clint Dempsey.
Former Arsenal forward Emmanuel Adebayor also starts along with Jermain Defoe in a game the Spurs are pushing to win at the Emirates Stadium.
Meanwhile, first choice keeper Wojciech Szczesny has now recovered from the ankle injury which has kept him out of action since September 15 and starts today.
Arsene Wenger has also gone with strikers Olivier Giroud, Lukas Podolski and Theo Walcott and midfielder Mikel Arteta in his starting team.
Midfield playmaker Jack Wilshere returns to the Arsenal side after missing the 3-3 draw against Fulham because of suspension and his return meant Francis Coquelin is back on the bench, along side Vito Mannone, Alex Oxlade-Chamberlain and Aaron Ramsey.
Arsenal v Tottenham Teams
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Subs: Mannone, Andre Santos, Oxlade-Chamberlain, Ramsey, Coquelin, Arshavin, Jenkinson
Tottenham: Lloris, Walker, Gallas, Vertonghen, Naughton, Lennon, Sandro, Huddlestone, Bale, Adebayor, Defoe
Subs: Friedel, Dempsey, Dawson, Sigurdsson, Livermore, Townsend, Carroll
Referee: Howard Webb