Initial reports suggest the 26-year-old could be out of action for six weeks - and that would rule him out of the opening two games of this year's Six Nations.
England open up their campaign against Scotland on February 4 before tackling Italy a week later.
Leicester director of rugby Richard Cockerill told the Daily Mail: "Toby has had a bang on the knee and it's being treated. We'll just have to wait and see how it progresses."
If Flood is ruled out, then it would open the door for in-form Saracens star Owen Farrell to make his international debut.
England also have doubts over Flood's club-mate Manu Tuilagi, while fellow Tiger Louis Deacon has already been ruled out of the championships.
Tuilagi and Deacon both suffered hamstring injuries in the win over Worcester. While 20-year-old centre Tuilagi could be back in action within a month, lock Deacon is facing a longer spell on the sidelines.
England's interim head coach Stuart Lancaster will confirm his 32-man squad for the tournament on January 11.
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