Juve hold a 1-0 advantage from the first leg at the Stade de Gerland, which saw the Serie A leaders net a crucial away goal in the 84th minute through Leonardo Bonucci.
Bouncci's strike puts Antonio Conte's men in command of the tie, and the Turin club should be clear favourties to qualify for the last four considering their magnificent home record.
Indeed, the second leg takes place a year to the day since Conte's side last suffered a home defeat, which came at the hands of Bayern Munich in the second leg of last season's UEFA Champions League quarter-finals.
The likes of Real Madrid, Napoli and Roma have all failed to win in Turin since that day, and Lyon coach Remi Garde, who said Lyon had a "mountain" to climb before the first leg, accepted his side needed a "miracle" following its conclusion.
"It was a great experience for the young players (playing against Juve)," he said. "It will be tough in Turin and we will need a miracle to win in the second leg."
The clash marks the start of an exciting run of fixtures for Lyon, who face Ligue 1 champions-elect Paris Saint-Germain on Sunday before taking on Laurent Blanc's men again in the Coupe de la Ligue final the following Saturday at the Stade de France.
But the seven-time French champions will approach that daunting triumvirate of fixtures with a number of injury concerns.
Clement Grenier is out with a groin problem, and fellow midfielder Gueida Fofana will also miss out with a similar injury.
Playmaker Yoann Gourcuff remains unavailable with an ankle problem, and Jordan Ferri - scorer of a spectacular long-range strike in Sunday's 2-1 win at Valenciennes - will likely be selected to fill the void again in a depleted midfield.
At the back, Mouhamadou Dabo has yet to recover from a hamstring issue and Miguel Lopes is out for the rest of the season with a broken leg.
Meanwhile, Juventus will be boosted by the return of Arturo Vidal after he missed the 2-0 Serie A win over Livorno at the weekend through suspension.
Defender Andrea Barzagli (calf) is still struggling for fitness, but Carlos Tevez shook off a thigh injury to play against Livorno on Monday and defender Angelo Ogbonna is available to feature for the first time in nearly a month.
