The Nittany Lions host Miller and the ninth-ranked Buckeyes on Saturday.
"One of the keys to the game is to do the best we can to contain him and tackle him. And at the end of the day he's going to make plays," O'Brien said Tuesday. "And when he makes a play, we have to play the next play. We have to keep him out of the end zone the best we can. ... This is an excellent player who has had a heck of a season."
Miller is a dual-threat quarterback at Ohio State. He has completed 58 percent of his passes this season for 1,384 yards, 11 touchdowns and five interceptions.
On the ground, Miller leads the team with 959 yards rushing on 141 carries. He averages 119 yards per game and has scored 10 rushing touchdowns.
O'Brien said his defensive line has to be disciplined in how they rush the passer.
"And if they can do that, they have a chance. But, again, at the end of the day this guy's going to make plays," O'Brien said. "And we're not going to shut this guy down totally. This is an excellent football player, and we just have to make sure that we show up and do the best we can on Saturday night."
Kickoff is 5:30 p.m.