The Spaniards are guaranteed to finish at least second in Group F but will overtake Bayern Munich if they manage a better result in Lille than Bayern achieve at home to BATE Borisov.
Valencia's form in Europe has not been matched in the Primera Division, and coach Mauricio Pellegrino paid the price on Saturday after a 5-2 defeat by Real Sociedad.
Pellegrini had only been in charge since May but the Los Che board lost patience with the club 11th in the table, although they are only four points off a Champions League place.
Former Athletic Bilbao, Espanyol, Villarreal and Olympiacos coach Valverde took over the reins on Monday after signing a deal until the end of the season.
The 48-year-old immediately set his sights on qualifying for the Champions League again but finds himself in an unusual position.
He told www.valenciacf.com: "This is the first time that I've taken charge of a team in the middle of the season. It is definitely not going to be an easy task and never is when a manager joins a team under these circumstances.
"I don't want people to take me saying that there is a problem as an attack on anyone. I think that would be showing a lack of respect to the previous manager and I don't want to do that. I respect him immensely.
"There is a good squad here, capable of doing good things. I will try to transmit the idea of Valencia that I have to the players and the possibilities that they have.
"Our aim is to get into the Champions League and that continues to be so."
The visitors will be without defender Joao Pereira, who is struggling with a calf problem, while striker Roberto Soldado is suspended.
Lille have had a miserable time in the Champions League this season and are already guaranteed to finish bottom of the group, although they did get off the mark with victory over BATE last time out.
Salomon Kalou should be available for Rudi Garcia's side following injury, while Marvin Martin has also been declared fit after a bruised back.
Ryan Mendes continues his recovery from tendonitis in his ankle, but Djibril Sidibe and Benoit Pedretti are suspended.
Tulio de Melo is out of action with a hamstring strain.