Valencia's hopes of a winning return to Europe's elite club competition after a two-year absence were dashed when they were beaten 3-2 at home by Zenit St Petersburg in their opening game two weeks ago.
Lyon were held to a 1-1 draw at Belgian side Ghent, who travel to Russian champions Zenit in Tuesday's other game in the section.
"It's not going to be decisive or definitive but we are aware that we have to get some points on the board here and the match is of maximum importance," Nuno told a news conference on Monday previewing the clash at the Stade de Gerland.
"When we talk about competing, we talk about winning," added the Portuguese, who has come under pressure after Valencia made a disappointing start to the season in both La Liga and Europe.
Valencia, Champions League runners-up in 2000 and 2001, have a decent away record against French clubs in Europe, losing only twice in 11 matches and winning four.
In their most recent campaign in 2012-13, they beat Lille home and away in the group stage but fell to Paris Saint Germain in the round of 16.
Nuno said Valencia's Australia goalkeeper Mat Ryan was available to face Lyonnais after recovering more quickly than expected from a knee problem.
Ryan, who joined the La Liga side in the close season, had arthroscopic surgery at the end of last month to correct a problem with the meniscus in his right knee.
(Writing by Iain Rogers, editing by Pritha Sarkar)
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