Hixon was injured when his right knee appeared to buckle on a juggling touchdown catch in the second quarter of Monday night's win over the Rams.
Afterward, the wide receiver thought he had a calf injury.
"It was kind of wishful thinking more than anything," Hixon said Wednesday, one day after he had an MRI on the knee.
Hixon tore the same ACL last summer and missed the entire 2010 season. He had four catches for 50 yards in two games this season and was also the team's primary punt returner, but is looking at another prolonged period of recovery.
Surgery will take place in the near future, after which Hixon is likely to be placed on injured reserve. He would be the ninth Giants player to be placed on IR this season.
"I'm going to be back," Hixon said. "I felt like I was better when I came back this time. We'll just have to do it again and add another chapter to the book."
Fellow wide receiver Mario Manningham was examined by an independent neurologist and team doctors on Tuesday as he tries to recover from a concussion. He will undergo further examination and testing during the week.
The banged-up Giants play at NFC East rival Philadelphia on Sunday.