The French side have lost their opening two games in this year's competition, conceding five goals in the process, while Valencia sit second, ahead of Chelsea on goal difference.
The club from the Belgian border have kept just two clean sheets all season, with their defence increasingly caught out when sides go on the counter against them.
Although Lille are not quite the free-flowing attack force they were last season when Nicolas Pepe was so influential, they have still got real pace and talent in the shape of Jonathan Bamba, Jonathan Ikone and Victor Osimhen.
The Nigerian was named Ligue 1 Player of the Month for September after taking his league goal tally in the league to seven for the season, and he will be key to any hopes the French side have of registering a win.
Osimhen has proved a constant threat from set pieces and through balls, while he is also one of the leading shot takers in France this season, averaging just shy of four per game.
Encouragingly for Valencia, however, is the fact that Lille have never beaten a Spanish side before in European competition.
Traditionally operating with a 4-4-2 or a 4-1-4-1, Los Che have been largely difficult to break down but they have also struggled for goals, scoring just 14 in 11 competitive matches this season.
That lack of scoring prowess is even more magnified in the Champions League, where the Spaniards have drawn a blank in seven of their last 11 games.
Without influential left-back Jose Gaya, Valencia will be reliant on Daniel Wass, Ferran Torres and Denis Cheryshev for creativity in wide areas, while they will be hoping that Rodrigo is able to continue his good recent form for club and country to help them secure a second win of this year's group stage.
Lille recent form: LL
Lille recent form (all competitions): DWDLDL
Valencia recent form: WL
Valencia recent form (all competitions): DDWLWD
Former Swansea City and Bayern Munich midfielder Renato Sanches is one of three injury absentees for Lille on Wednesday.
Also out are Zeki Celik and Timothy Weah, although the former was the only one of the three likely to actually start the game. Jeremy Pied is expected to deputise in his continued absence with an ankle problem.
Galtier is likely to make a few changes from the side that lost at the weekend, with Thiago Maia coming into defensive midfield and dead-ball specialist Yusuf Yazici likely to be favoured to Luiz Araujo in what could be a close game potentially decided by a set piece.
Gaya is the only injury absentee for Valencia, with Kevin Gameiro now back in action after his recent groin troubles.
Given that Valencia will fancy their chances of getting something from this game they are likely to opt for a 4-4-2, a formation that allows them to incorporate someone like Geoffrey Kondogbia but also both Rodrigo and Maxi Gomez up front.
Lille possible starting lineup:
Maignan; Pied, Fonte, Gabriel, Bradaric; Soumare, Maia; Ikone, Yazici, Bamba; Osimhen
Valencia possible starting lineup:
Cillessen; Wass, Garay, Gabriel Paulista, Costa; Torres, Kondogbia, Parejo, Cheryshev; Gomez, Rodrigo
We say: Lille 1-1 Valencia
Although Lille are capable of producing the better football, they are yet to fully click this season and Valencia's more direct style of play should be enough to secure them an important point heading into the second half of the group stage.