Rudi Garcia's side have shown they can fight above their weight this season.
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Memphis Depay's return from injury could be crucial as Lyon look to battle past Juventus and into the UEFA Champions League quarter-finals.
Season so far
Form guide: W3 D2 L2 F10 A8
Top scorer: Memphis Depay (5)
Their campaign in ten words: A team that never surrender and punch above their weight.
Group G runners-up
▪ Lyon 1-1 Zenit (Depay 51pen; Azmoun 41)
▪ Leipzig 0-2 Lyon (Depay 11, Terrier 65)
▪ Benfica 2-1 Lyon (Rafa Silva 4, Pizzi 86; Depay 70)
▪ Lyon 3-1 Benfica (Andersen 4, Depay 33, Traoré 89; Seferović 76)
▪ Zenit 2-0 Lyon (Dzyuba 42, Ozdoev 84)
▪ Lyon 2-2 Leipzig (Aouar 50, Depay 82)
Round of 16
First leg (26 February): Lyon 1-0 Juventus (Tousart 31)
Bruno Guimarães, Lucas Tousart and Houssem Aouar powered a fine performance from midfield, a solid and disciplined Lyon upsetting the pre-match predictions by beating Juventus for the first time in the club's history.
Expert view: David Crossan, UEFA.com Lyon reporter
Lyon should be stronger than when they overcame Juventus in the first leg back in February because the long delay has allowed important attacking weapons Memphis Depay and Jeff Reine-Adélaïde to recover from long-term knee injuries.
Who’s in charge?
After winning a double with Lille in 2011, Rudi Garcia led Roma to a second-placed finish in Serie A. He also took Marseille to the 2018 UEFA Europa League final after returning to France two years previously (they lost to Atlético Madrid in Lyon). Garcia then joined OL in May 2019.
Key quote: "For me, football is a show. If we play well, we will win matches. There must be a hatred of losing, and one has to play to win."
Garcia likes to use an attack-minded 4-3-3 formation, but is canny enough to adapt his team to counter opponents' strengths. His Lyon side can operate a more reserved 4-2-3-1 or a 3-5-2, as they did in the round of 16 opener against Juve. Midfield is the key, with the skill, game awareness and quick passing of Guimarães and Aouar central to Lyon's success.
Star player: Memphis Depay
The ex-Manchester United forward has scored five in as many UEFA Champions League fixtures this season, plus nine in 13 Ligue 1 matches. A knee injury last December stopped him in his tracks, but his return could make the difference in the remaining games of the campaign.