Cruz was ruled out for Sunday's game at Detroit after undergoing an arthroscopic debridement of his left knee Thursday. Cruz suffered the injury and a concussion during Sunday's loss to the Seahawks.
"Very, very unfortunate," Coughlin said of Cruz's injury. "Victor was having a good year. It would have been great to have him for these last two games.
"We are very confident that the swiftness with which the procedure was done should give him an outstanding opportunity in the offseason to be stronger than ever."
Coughlin also will not have defensive end Jason Pierre-Paul (shoulder), running back Peyton Hillis (concussion) and safety Cooper Taylor (hamstring) against Detroit. They were ruled out. Guard David Diehl (knee) is doubtful after not practicing Friday. Guard James Brewer (ankle) and wide receiver Jerrel Jernigan (knee) are questionable after being limited in practice.
Cruz was cleared of his concussion and passed the NFL protocol, but the knee injury effectively ended his season. The Giants haven't placed Cruz on injured reserve. The wide receiver will finish with 73 receptions for 998 yards and four touchdowns.
He was injured when he went up high to catch a pass and came crashing down on his head while being tackled in the third quarter against Seattle. The 16-yard reception was initially ruled a catch but eventually overturned on a challenge.
Cruz, 27, had gone over 1,000 yards receiving in his previous two seasons since becoming a starter. He signed a five-year, $43 million extension after fighting for a lucrative contract in the offseason.
With Cruz out, Eli Manning will turn to Hakeem Nicks, Rueben Randle and Jernigan. Nicks is in a contract year and has struggled at times with just 50 catches for 794 yards. He will be looking to score his first touchdown of the season against Detroit.
Randle, the team's second-round pick in 2012 out of LSU, will have an opportunity to show if he can fill Nicks' shoes if Nicks doesn't return next season.
"I am trying," Randle said of proving he can be a full-time starter next season. "I don't know if I have [shown that yet] or not. That is definitely the case that I am trying to prove."
Randle, who has 37 receptions for 571 yards and six touchdowns this season, is hoping to finish the season strong like he did last year. He had four catches for 58 yards and two touchdowns in the season finale against Philadelphia last year as a rookie.
"Just boosted the confidence a little bit," Randle said of that game. "Just let the coaches know what I can do, prove to those guys and to the teammates the type of player that I am."