BEIJING >> Rafael Nadal was knocked out of the China Open in his third match back from an extended injury layoff, falling to big-hitting qualifier Martin Klizan of Slovakia 6-7 (7), 6-4, 6-3 on Friday.

The second-seeded Spaniard struggled with Klizan’s power game and his own consistency in the quarterfinal, finishing with an uncharacteristic 37 unforced errors and just 21 winners.

Nadal said an upset like this was natural “when one player plays bad, plays without rhythm, no confidence on the shots, having more mistakes than usual, being not confident how to play the points, and how to win the points.”

Novak Djokovic and Andy Murray, meanwhile, set up a semifinal showdown with convincing wins over two young players enjoying breakthrough seasons.

The top-seeded Djokovic defeated Wimbledon semifinalist Grigor Dimitrov of Bulgaria 6-2, 6-4, while sixth-seeded Murray took out U.S. Open champion Marin Cilic 6-1, 6-4.

On the women’s side, defending champion Serena Williams withdrew before her quarterfinal against Samantha Stosur with a left knee injury that raised doubts about her ability to play the WTA Finals in Singapore this month.

In his first tournament since Wimbledon because of a wrist injury, Nadal looked sharp in his first two matches in Beijing and, against Klizan, he even led 7-6, 4-2 with a break point. But after the Slovak won that game, he turned around and broke Nadal twice to take the set.

“For me, this victory was the best night in my life,” Klizan said. “I’m just very happy that I beat a legend.”

Nadal said he knew it would be difficult to return to the tour during the hard-court Asian swing, where the courts are quick and the draws loaded.

“I am going to work hard with the right attitude to play better than what I did today,” he said. “I will be happy if I finish the season and I am able to take a one-and-a-half-week holiday, then practice for one month in perfect conditions to try to start the next season with positive feelings.”

Djokovic’s patience and experience showed against the fifth-seeded Dimitrov, who broke the Serb twice in the second set but was unable to build on the momentum, making costly errors to give the breaks right back.

Djokovic said that while younger players like Cilic, Dimitrov, U.S. Open finalist Kei Nishikori and Wimbledon semifinalist Milos Raonic are improving quickly, he believes it will still be a while before there’s a changing of the guard in men’s tennis.

“It’s logical to expect that in the sport, after so many years of dominance by three, four players, there are some others who are coming up,” said the Serb, who improved to 22-0 at the China Open. “But on the other hand, it’s still not happening that they are the ones who are winning Grand Slams and being top three, four in the world.

“It takes time. How long? I don’t know. I’ll make sure that they don’t come any time soon.”

Murray is enjoying his best stretch since back surgery last autumn and missing several months of the season. He lost a close four-set match to Djokovic at the U.S. Open and captured his first title since his 2013 Wimbledon triumph last week in Shenzhen.

He’s hoping to carry that momentum into Saturday against Djokovic, who holds a 13-8 advantage in their series.

“He’s never lost (in Beijing), which is impressive. I’m aware it’s going to be an extremely difficult match,” Murray said. “If I play like I did at the U.S. Open, I’ll definitely give myself an opportunity.”

Third-seeded Tomas Berdych will play Klizan in the other semifinal after beating John Isner of the U.S. 6-1, 6-4.

On the women’s side, Williams said the pain was so bad in her knee during her three-set win over Lucie Safarova on Thursday, she had no choice but to pull out.

“It throbs just sitting, standing,” she said. “I felt it mostly serving because I’m landing on my left knee. That was really killer for me.”

Williams said she will go to Europe for a knee exam to determine the extent of the injury, and whether she can play the WTA Finals.

“If I feel this way for Singapore, I don’t think it’s smart for me to play,” she said. “I’m just going to see how it goes.”

Williams was joined on the sidelines by second-seeded Simona Halep, who withdrew before her quarterfinal against Ana Ivanovic with a hip injury.

Ivanovic next faces Maria Sharapova, a 6-0, 6-4 winner over Svetlana Kuznetsova, while Stosur meets Petra Kvitova, who defeated Roberta Vinci 7-6 (2), 6-4.