Giants head coach Pat Shurmur told reporters that Collins will "most likely require surgery," but noted a final decision has not been made on the status of the 24-year-old for the rest of the season.
Collins sustained the injury during Sunday's 30-27 overtime win over the Chicago Bears. He has been ruled out as the Giants (4-8) bid for their fourth victory in five outings on Sunday against the host Washington Redskins (6-6).
A two-time Pro Bowl selection, Collins has recorded a team-leading 96 tackles and one forced fumble through 12 games this season. The 6-foot, 222-pound Collins has collected 437 tackles, eight interceptions and four sacks in 59 career contests since being selected by the Giants in the second round of the 2015 NFL Draft.
Collins is in the final year of his contract and is eligible to become a free agent in 2019, unless the Giants designate him as a franchise player or sign him to a contract extension ahead of the league's new calendar year.
With Collins injured, New York likely will look to fellow safeties Curtis Riley, Michael Thomas and Sean Chandler.