The Irons managed to secure a 1-1 draw with the French giants at a rocking London Stadium last week despite Aaron Cresswell's red card.
The decisive moment came just before half-time when Cresswell was controversially sent off for a challenge on Moussa Dembele.
Despite that, Jarrod Bowen gave West Ham the lead before Tottenham loanee Tanguy Ndombele restored parity for Les Gones.
Lyon v West Ham: talkSPORT commentary
This Europa League quarter-final second-leg will take place on Thursday, April 14.
talkSPORT will have live coverage of the clash at Parc Olympique Lyonnais with kick-off scheduled for 8pm.
Hugh Woozencroft will be your presenter while commentary will come from Jim Proudfoot and former West Ham defender Alvin Martin.
To tune in to talkSPORT or talkSPORT 2, click HERE for the live stream.
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Lyon v West Ham: Team news
The hosts' first choice goalkeeper Anthony Lopes was taken off at the weekend, while Ndombele and Houssem Aouar are also struggling with injuries.
Lyon are already without the likes of Maxence Caqueret, Thiago Mendes, Rayan Cherki, Lenny Pintor and Sinaly Diomande.
West Ham are missing Cresswell through suspension and have since seen Kurt Zouma succumb to an ankle issue.
Angelo Ogbonna remains a long-term absentee but Manuel Lanzini is back from a ban that forced him to miss the first-leg.
Lyon v West Ham: What has been said?
Describing first-leg referee Felix Zwayer as 'a clown', Jason Cundy told The Sports Bar: "I don't even think it's a foul [from Cresswell].
"I can't believe the referee, he was a shocker. The referee was shocking.
"Everyone slaughters the referees that we've got here in the Premier League. I've said this for years, I think that we've got the best referees in the world, I genuinely do.
"They make big mistakes sometimes, but I see what goes on on the continent and some of the debacles that go on.
"I don't think there's actually a foul. I honestly don't think it's a foul, let alone a red card. The referee could have played on. He touches his arm, he doesn't drag him or pull him, Dembele goes over, cons the referee and the referee cannot wait to get the red card out.
"They've been mugged off there, West Ham."