The Romanian will face 22-year-old Coco Gauff in the last four, after the American overcame Russian teenager Mirra Andreeva 4-6 6-2 6-4.
Cirstea, who plans to retire later this year, has already delivered the shock of the tournament by stunning world No.1 Aryna Sabalenka in Saturday's third round.
She now stands just one win away from breaking into the top 20 for the first time in her career, having previously reached a career-high ranking of 21 in August 2013.
"I always said there's no expiration date for ambition and dreams," said Cirstea, the 26th seed in Rome.
"I think everyone can see that I absolutely love this sport. I have so much passion for it. For me to play here and be in the semi-finals in Rome is absolutely amazing.
"I'm so grateful to the sport. I'm just really, really enjoying my week in Rome so far."
Cirstea's remarkable claycourt form has seen her suffer only two defeats this season on the surface - against two-times major winner Gauff at the Madrid Open and Andreeva at the Linz Open.
She also withdrew from the Open de Rouen semi-finals due to a leg injury.
Gauff came from a set down for the third consecutive match in Rome, and maintains her perfect record against Andreeva with her fifth win in five meetings.
After losing the opening set, Gauff raced into a 3-0 lead in the second, saved a break point at 3-1 up and broke to wrap up the set and force the decider, where the American held off a comeback charge from the Russian.
Gauff failed to serve out for the match at 5-1 up, and again at 5-3, before breaking Andreeva to seal the win.
"I had a big lead in the third set and it got a little bit close," Gauff said.
"She's a great player, she's capable of winning games and I think I learned a little bit on how to try to close those out but I'm glad I was able to win."
