The Russian has not dropped a set all week, beating eighth seed Stan Wawrinka 7-5, 6-3 in the first round and British qualifier Cameron Norrie 6-2, 6-2 in round two. Tsitsipas has had to work hard for his two victories, defeating Egor Gerasimov 7-6 (5), 7-5 and Hubert Hurkacz 6-4, 4-6, 7-5.
This is the third career meeting between Khachanov and Tsitispas with the Greek having won both prior matchups at the 2017 and 2018 Rolex Shanghai Masters.
The match will be the first singles match to be played on Center Court with the winner facing either French qualifier Jeremy Chardy or sixth seed Andrey Rublev in the semifinals.
Khachanov will look to dictate this match with his serve and forehand while Tsitsipas will want to attack with his backhand. Whoever gets control of the baseline will have the upper hand in the majority of the rallies.
The movement of the second seed could also play a factor and while Khachanov certainly doesn't move poorly for a man of his size, Tsitsipas is the better of the two moving around the court. What the Greek must worry about is not getting blown away by the power of the world number 21.
Khachanov is certainly a better player than the last time he played Tsitsipas, but the second seed, despite not looking his best all week, still has to be given the edge since he's been in these pressure moments more often.
It will be a close match as that just seems to be the way Tsitsipas has played all week, but expect him to prevail in what should be the best match of the four quarterfinals to be played today.
Prediction: Stefanos Tsitsipas in three sets