Osimhen scored the opener in the 25th minute at the Mestalla for his second in the champions league this season and his ninth goal in sixteen appearances for Lille in all competitions.
The 20-year old restored to the starting lineup after fully recovering from the injury sustained a couple of weeks ago against Bordeaux which put an end to his record breaking run of scoring in all home games in Ligue 1 had previously not scored away from home for the Great Danes in seven previous appearances in all competitions.
Valencia, however, rallied back with four second-half goals including three in eight minutes to turn the tie on its head and grab all three points leaving Lille in search of a first win in the competition.
Captain Daniel Parejo set the tide turning with a 66th-minute equaliser from the spot before a blitz of three goals in eight minutes from Adama Soumaoro, Geoffery Kondogbia and Ferran Torres completed the comeback.
Christophe Galtier’s side remain bottom of Group H behind leaders Chelsea who came back from 4-1 down to draw 4-4 with second-placed Ajax at Stamford Bridge.
Osimhen will hope to continue his goalscoring form for Lille when they entertain FC Metz at the Stade Pierre-Mauroy at the weekend before the international break where he will lead the line for the Super Eagles in the 2021 AFCON qualifiers against Benin and Lesotho.