The start comes one day shy of the one-year anniversary of Matsuzaka undergoing Tommy John ligament transfer surgery, a procedure which at least raised the question of whether he would ever throw another pitch for the Red Sox.
Matsuzaka's contract expires at the end of 2012.
"Saturday's game will be a special game. It will present a new step for me," Matsuzaka said. "It is going to be a very emotional day, but I have to remain calm and treat it like any other start I've had throughout my career."
This will be the first of Matsuzaka's 106 Major League starts not to be managed by Terry Francona. Instead, he will now pitch for Bobby Valentine, a man who managed against him in Japan before calling some of his Red Sox games as an ESPN broadcaster.
"It's hard to predict what's going to happen," Valentine said. "I hope he throws strikes, and I hope he has more than two pitches to do it with, and I'd be happy if that happened."
Valentine is trying not to hold any grand expectations for Dice-K.
"Again, I don't have anything to compare it to," Valentine said. "I've seen some of his games. I thought they were terrific. I'd like him to pitch like some of his past terrific games. I don't want to generalize on what he was or can be. Let's just take it as his first start in 2012, and then we'll talk about it."