Rublev had two fairly easy victories over Marcos Giron and Andy Murray to begin the event before a three-set thriller against French qualifier Jeremy Chardy that lasted two hours, 42 minutes.
Tsitsipas has been made to work hard for his semifinal spot. After a 7-6 (5), 7-5 victory over Egor Gerasimov in the opening round, the Greek has had to go three sets in his last two matches against Hubert Hurkacz and Karen Khachanov, winning 7-5 in the decider in both.
This is the sixth career meeting between Rublev and Tsitsipas with the Greek holding a 3-2 edge. Their last meeting was at the round robin stage of the 2020 Nitto ATP Finals with Tsitsipas coming out on top 6-1, 4-6, 7-6 (6).
The match will be second on Centre Court following the first doubles semifinal with the winner facing an unseeded player in the final: either Borna Coric or Marton Fucsovics.
This is a match that will be won from the baseline. Rublev loves to play power tennis and want look to dictate mainly with his serve and forehand. Tsitsipas will predominantly look to use his backhand to dictate rallies.
The Russian will want to play mostly shorter rallies, although his game has evolved to the point where he is more comfortable in longer rallies, but that edge mainly still goes to Tsitsipas in this match. Rublev also has an advantage with his serve.
Tsitsipas will be well-prepared for this contest having already faced big hitters and big servers in Hurkacz and Khachanov and he has a consistent baseline game that can force errors out of Rublev, something he's been able to do in the past.
The second seed is also still the better mover of the two, but will need to do a good job protecting his second serve as the fourth seed will look to attack at every chance he gets.
Rublev is playing better than Tsitsipas at the moment. He's controlling his power, is confident and has gotten through the big moments well while the Greek has found a way, but is not as consistent as he usually is and should have lost to Khachanov.
The Russian has lost his last two to Tsitsipas, but he'll fancy his chances here. With both players knowing this is a tremendous opportunity to win an important title, look for Rublev to come out on top in what should be a terrific affair.
Prediction: Andrey Rublev in three sets