The injury came with 1:17 left in the first on a third-down screen pass to Warrick Dunn.
The Giants will lose Hamilton for the remainder of the season, and that hurts.
Left DE Michael Strahan left prior to the half with back spasms, but returned.
The only remaining healthy starter left on the field was DT Cornelius Griffin.
Backup DT Lance Legree, a second-year player out of Notre Dame, will start in Hamilton's place. Legree started two last season when Hamilton was resting a nagging shoulder injury.
Overall, the Giants defensive line is painfully thin, and it's likely the team will look for roster additions to fill the gap.