"Wales may have lost seven in a row, but I don't think they'll be nervous at all. It's obviously a massive game for us. Wales are very tough opposition. The set-piece and breakdown will be massive," he predicted.
"Wales has become a championship-defining match. You can't win a Grand Slam on the first day, but you can lose one if you don't make a good start," O'Brien added.
The abrasive back row admitted Ireland go into the match determined to break their recent duck against Wales which has seen them lose three games on the trot.
"There's a bit of hurt on our part after losing the last three and we want to put that right," said O'Brien. "Things didn't go our way last year, which was unfortunate because we played so well at times during the game. But we didn't play for the full 80 minutes, which is what we're looking to do this time."
The outcome could be settled between the two outside halves where Dan Biggar and Jonathan Sexton will go head to head.
The Ospreys fly half has been recalled to the Wales starting XV and is eagerly awaiting his duel with the classy Irishman.
"I could sit here all day and say how good a player Sexton is," said Biggar. "I am really looking forward to going up against him. I have played against him many times, and he's right up there on top of his game at the minute.
"It is a real challenge and privilege to play against him when he's playing as well as he is. He is a great player and he has got great players around him, which is always nice for a 10. It makes your job easier when you have got centres like (Gordon) D'Arcy and (Brian) O'Driscoll outside you.
"But we have got a pretty good back line with the likes of Jamie Roberts and Jonathan Davies. They have got pedigree as well. It's exciting.
"We had a poor autumn - there is no hiding away from it. But this is a new campaign with new strategies in place, and it's something we are looking forward to.
"We have got to do the simple things well. International rugby is about doing that, about making your set-piece and ensuring your kicking game and defence is in order. You get those three things right, and you stand a good chance of winning games of rugby."