Australian Open champion Stanislas Wawrinka suffered his first defeat of the season, leaving Novak Djokovic and Roger Federer as the last big names standing at the BNP Paribas Open.
Third seed Wawrinka went down 7-6 (7/1) 4-6 6-1 to South Africa's Kevin Anderson, while Djokovic looked in deep trouble after losing the first five games to Marin Cilic.
The Croatian was the first man to reach 20 wins at tour level this season but Djokovic recovered to triumph 1-6 6-2 6-3 and will face France's Julien Benneteau in the quarter-finals.
Djokovic is the only member of the world's top seven to reach the last eight, but Federer has been the man in form.
The Swiss is yet to drop a set at the tournament and extended his winning run to nine matches with a 6-4 6-4 victory over his good friend Tommy Haas.
Federer and Wawrinka, who reached the semi-finals together in the doubles on Wednesday night, had been on course to face each other in singles, but instead Federer will play in-form Anderson.
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.
The Swiss admitted coming back from winning the Australian Open had taken its toll mentally.
He said: "For sure he (Anderson) is 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 his upset of 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.
In the women's tournament, second seed Agnieszka Radwanska came through a topsy-turvy battle against Jelena Jankovic to reach the semi-finals.
Radwanska won a marathon opening set only for Jankovic to fight back, and the Serbian then recovered from 0-4 to level in the decider but Radwanska pulled away again to win 7-5 2-6 6-4.
The Pole next meets Simona Halep, who was the first woman through to the last four after continuing her fine run of form with a 6-2 6-2 win over Casey Dellacqua.
The sixth seed had to battle 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."
Halep is guaranteed to rise to world number five whatever the result of her semi-final, meaning she will become the highest-ranked Romanian in the history of the WTA.