With Memphis Depay injured and seemingly out for the rest of the Ligue 1 season, Lyon are seeking a replacement to strengthen their attacking options.
Ekambi, who previously played in France with Paris FC, Sochaux and Angers, has caught Lyon's attention and Spanish newspaper AS reported an initial €12million offer has been turned down.
That led Villarreal boss Javi Calleja to say on Thursday that any club wanting the striker must consider his release clause, which is said to be over €60million.
"There has been real interest," Calleja said in a news conference, according to Marca.
"The player has not trained in recent days because of physical problems, not because of this interest.
"Ekambi has a release clause, a value in the transfer market, and those that want him have to accept that."
Ekambi, 27, is a Cameroon international and joined Villarreal from Angers in 2018.
He was Villarreal's leading scorer in LaLiga last season and has netted six goals in 18 league appearances this term.
Lyon are toiling in 12th place in Ligue 1 at the midway point of the season, seven points adrift of the top three.