Australian Open champion Stanislas Wawrinka suffered his first defeat of the season to join the exodus of top names from the BNP Paribas Open.
The Swiss third seed lost 7-6 (7/1) 4-6 6-1 to South Africa's Kevin Anderson, leaving Novak Djokovic as the only one of the world's top seven still in with a chance of making the quarter-finals.
Wawrinka took a month off after his shock win over Rafael Nadal in Melbourne but had looked to have carried his form through, losing just two games to Andreas Seppi in the third round in Indian Wells.
Wawrinka received treatment off court at the end of the first set but then roared back after going a break down in the second.
He immediately fell behind at the start of the third, though, and Anderson ensured the end was swift in coming.
The 18th-ranked South African is in the best form of his life having reached the final of his last two tournaments in Delray Beach and Acapulco.
Wawrinka played down concerns over a back injury, saying: "It's just tightness and I was a little bit nervous and tight and tired. That was nothing to do with the result today."
Wawrinka admitted coming back from winning the Australian Open had taken its toll mentally.
He said: "For sure he's playing good. He's a tough player to play in fast conditions. But I'm more disappointed with myself. I felt I was tired mentally.
"I think I was negative all match. I was complaining a lot about my serve, about the way I was playing, and with that, I don't deserve to win matches.
"Mentally it's not easy what's happened in the past few months. It's tough for me. It took me a lot of energy to come back here and practise well."
It will be a very different looking quarter-final line-up to what has been witnessed at Masters series events for the last few years, and Milos Raonic believes that is partly down to Wawrinka.
Tenth seed Raonic came from a set down to defeat Wimbledon champion Andy Murray 4-6 7-5 6-3.
He said of Wawrinka's Australian Open triumph: " I think everybody in that top-10 range, also a little bit outside trying to breakthrough, took a deep breath and said, 'Why can't that be me?'
"Guys don't feel like they're facing somebody that's invincible. They feel a little bit more vulnerability against those top guys, and they just have to exploit that.
"They know that the window is still very small, but at least they see a window of opportunity."
Next up for Raonic is Ukraine's Alexandr Dolgopolov, who followed up his upset of Rafael Nadal by defeating Italian number one Fabio Fognini.
Ernests Gulbis is another player to have begun to really make an impact at the top level and he won a bad-tempered clash with Roberto Bautista Agut 7-6 (7/0) 4-6 6-2.
Gulbis will now hope for a notable hat-trick - the other two times he has beaten Bautista Agut he has gone on to win the title.
The Latvian meets American 12th seed John Isner, who saw off Fernando Verdasco 7-6 (7/3) 3-6 6-3, in the quarter-finals.
Romanian Simona Halep was the first woman through to the semi-finals after continuing her fine run of form with a 6-2 6-2 win over Casey Dellacqua.
The sixth seed had to fight back from a break down in the final set to defeat Eugenie Bouchard in the fourth round, and although she was a much stronger favourite for this match, she said: " I had no pressure, and I was more relaxed than yesterday.
"I said that if I'm in the quarter-finals I have just to enjoy what I can do today, so I tried, and everything was going very well."