The world number five battled past Cristian Garin 6-3, 6-4 after one hour and forty minutes to reach the last eight.
Tsitsipas fired 17 forehand winners and won 75% of his net points (15/20).
This is his sixth trip to the quarterfinals this year.
“It was a really difficult task to complete. Cristian played good tennis and gave me a hard time out on the court,” Tsitsipas said in his post match interview. “I stayed composed and focused throughout the entire match.
— ROLEX MC MASTERS (@ROLEXMCMASTERS) April 15, 2021
“Things seemed not to be going my way towards the end of the second set, but I stepped back and left my mark. Things worked out well. I was fighting [and] I was putting my best performance out there. I was creating a lot of opportunities with my forehand and I think my serve paid off pretty well,” he added.
He will face Alejandro Davidovich Fokina for a place in the semifinals.