Ferguson: Hernandez out for up to four weeks
"I think it's torn ligaments in the ankle, it's looking like he'll be out for three to four weeks," the Scot told ESPN television.
The 23-year-old Hernandez, nicknamed 'Chicharito' and scorer of six league goals this season, was carried off on a stretcher after 12 minutes at Villa Park after turning his left ankle.
The injury was a blow for Ferguson ahead of Wednesday's key Champions League Group C game in Basel, when United, second in the Premier League, need to take a point against the Swiss side to reach the last 16.
"We're having a bad time with injuries at the moment," said Ferguson. "It's just as well we've a strong squad."
United travelled to Villa without striker Dimitar Berbatov, who has an ankle injury, while Brazilian twins Rafael and Fabio are also out.
Midfielder Tom Cleverley and striker Michael Owen are also sidelined, while Anderson has been ruled out until February with a knee injury.