Spurs made it to the round of 32 of the competition after qualifying from a group that also included Lazio, Panathinaikos and Maribor, while they have also impressed in the Premier League this season, taking 48 points from 26 matches to sit in fourth position in the table.
Lyon, meanwhile, overcame Ironi Kiryat, Athletic Bilbao and Sparta Prague to book their spot among the final 32 teams. Their league form has also been impressive this season, however, as they currently sit second in Ligue 1, six points behind leaders Paris Saint-Germain.
Spurs boss Andre Villas-Boas could recall Emmanuel Adebayor in attack with Jermain Defoe still out with an ankle injury, while Brad Friedel and William Gallas are also expected to be given valuable minutes on the pitch.
Lyon are expected to have Lisandro Lopez available after a slight knock in training, but Bafetimbi Gomis may have to make do with a place on the bench, with Alexandre Lacazette continuing alongside Lopez in attack.
Tottenham: Friedel; Walker, Dawson, Gallas, Naughton; Parker, Sigurdsson, Dempsey; Bale, Adebayor, Lennon
Lyon: Vercoutre; Reveillere, Dabo, Bisevic, Umtiti; Grenier, Gourcuff, Gonalons, Ghezzal; Lopez, Lacazette
Sports Mole says: 2-1