Mullens will replace Jimmy Garoppolo, who suffered a high ankle sprain last week against the New York Jets.
Giants coach Joe Judge knows what Mullens brings to the table.
“One thing he does an extremely good job of is you can spread the field out with him. He gets the ball out of his hand extremely fast. He’s a guy who turns two, as we say. The ball hits his hand, ball is coming out and he’s getting it to the receiver,” Judge said. “He has very good anticipation, he does a good job pre-snap really reading the defense, knowing where his receivers are going to be. He’s a tough, gritty dude. He obviously had some success for them in the past when he’s had to play.”
Mullens is a former undrafted free agent out of Southern Miss. The 25-year-old started eight games for the 49ers in 2018, including one against the Giants, with a 3-5 record.
The 49ers will also be without tight end George Kittle and running backs Raheem Mostert and Tevin Coleman.
Giants injury report
Doubtful: DB Adrian Colbert (quad)
Questionable: DB Brandon Williams (groin)