According to Ian Rapoport of NFL Network, Miller has a torn ACL and is out for the season.
Miller, 28, was injured on the Texans' second play on offense after he was hit just above the left knee by Dallas Cowboys tackle Maliek Collins. Miller was carted off the field to the locker room.
Following the game, Miller's head coach and quarterback both said that it was "tough to see."
"It's very tough. You have a guy who is so special to our team," Texans quarterback DeShaun Watson told reporters. "[When] anybody gets hurt, it's tough. But he's one of the guys that has a lot of energy and a lot of power for this team. And, I mean, it was tough to see him go off on the cart."
Added head coach Bill O'Brien: "It was a tough thing to see. It's very difficult to lose a guy like Lamar, for a lot of reasons. He's a great pro. He's just an awesome guy in the locker room."
Miller, a seven-year veteran who has spent the last three seasons in Houston as its feature back, is coming off his first Pro Bowl season in which he rushed for 973 yards, averaging 4.6 yards per carry, and five touchdowns.
The Texans traded for Cleveland Browns running back Duke Johnson Jr. on Aug. 8 and now the 25-year-old will likely see more action leading up to Week 1 against the New Orleans Saints.