Cascarino, who has made 56 appearances for France, ruptured her right ACL in a league win over Paris St Germain on Sunday.
"(Cascarino) underwent tests in midweek, which... revealed a partial rupture of the right anterior cruciate ligament," Lyon said in a statement.
The French club added that the winger will need to undergo reconstructive surgery and will be out "for several months".
"Unfortunately, I won't be able to take part in the World Cup this summer with my teammates, whom I'll be supporting from here," Cascarino said on Instagram.
France, who are also without Marie-Antoinette Katoto (24), will be looking to win their maiden World Cup at this year's showpiece event, which is being co-hosted by New Zealand and Australia from July 20th - August 20th.
They begin their campaign in Group F against Jamaica on July 23rd before facing Brazil and Panama.
