White Hart Lane side travel to the Stade Gerland.
Gareth Bale’s brace ensured Tottenham travel to Lyon leading 2-1 on aggregate.
Two stunning free-kicks from the Wales international handed Spurs a slender advantage, but the Londoners stressed their approach would remain the same at Stade Gerland.
“We are a team that normally score away from home so we hope to cancel out their advantage – we will set out the same way to try to attack,” insisted manager Andre Villas-Boas.
Former Lyon goalkeeper Hugo Lloris again appears set to miss out against his old club with Villas-Boas likely to opt once more for reserve custodian Brad Friedel, while England striker Jermain Defoe remains sidelined with an ankle problem.
Tottenham goalkeeper Brad Friedel will again start in the second leg of their Europa League clash with Lyon.
The 41-year-old has been used in the cup so far and will start ahead of ex-Lyon man Hugo Lloris.
Striker Jermain Defoe (ankle) has not travelled with the squad, but is expected to return to training next week.
Defoe’s absence will mean Emmanuel Adebayor will start up front for the Londoners.
Manager Andre Villas-Boas said of his striker: “He can still be the player we saw last season.
“We’re trying to unlock the best out of the player. Last year shows as an example for what we’re trying to get out of him.
“Strikers live off goals and we’re doing everything we can to try and unlock his full potential.”
Lyon coach Remi Garde believes Samuel Umtiti’s stunning goal in the first leg could prove crucial to their chances of making the next round.
“We know the away goal is very important,” said Garde, who took over as Lyon boss in 2011.
“We need to be patient. We have 90 minutes to qualify. It will be difficult but we can try to close them down and try to cut out their speed.
“To be able to qualify in front of the home fans would be exciting.
“We won (4-0 against Bordeaux) last weekend so we have a better mentality now.”
Tottenham: Friedel; Walker, Gallas, Vertonghen, Assou-Ekotto; Dembele, Parker; Lennon, Holtby, Bale; Adebayor.
Lyon: Vercoutre; Reveillere, Lovren, Bisevac, Umtiti; Gonalons, Fofana, Lacazette, Malbranque; Lopez, Gomis.
Tottenham 2/1 to win in Lyon: Lyon vs Tottenham Betting