The Russian 16th seed had lost six previous matches with Clijsters, who won Rome in 2003 but came into this edition well off her game.

Reclaiming the title would have seen the Belgian take over top spot in the world rankings from Amelie Mauresmo.

"I started missing from the start and just totally lost my confidence," confessed Clijsters, who said she could only begin training for Roland Garros in the wake of defeat.

"I couldn't do what I had to do, I didn't have the game to beat her in the second set. I tried to play like I had in our other matches, but it was an off-day."

Safina, younger sister of Marat Safin, had never won a set against Clijsters but this third-round upset victory came just days after the Belgian had won her first clay title in nearly three years with victory at Warsaw.

"I came to the court tired after a late doubles last night," said the 19th-ranked Safina.

"But I saw that she wasn't playing well, I told myself that I had to take my chances, I had to go for them.

"Kim is a great baseliner and she hits the ball hard. You just have to wait for any little chance you get and take it. It's really difficult to play her."

In the next round, Safina squares off against fellow Russian Elena Dementieva, the fifth seed, who advanced over German Anna-Lena Groenefeld 7-6 (7/1), 3-6, 6-1.

Venus Williams duplicated her best showing of the season with a quarter-final place after beating 2005 finalist Patty Schnyder 7-6 (7/2), 3-6, 6-1.

It was the American's seventh win without a defeat in that series and puts the former world number 1 into a match-up against Jelena Jankovic, who put out Katarina Srebotnik 7-6 (9/7), 6-1.

Italian qualifier Romina Oprandi, playing in only the second WTA event of her career, humiliated fragile Russian Vera Zvonareva 6-0, 6-1 the last eight

The defeat in 71 minutes was the most embarrassing of Zvonareva's career, her previous worst a 6-2, 6-0 hammering last year at the German Open by Czech Republic's Kveta Peschke.