Roger Federer stunned by John Millman in US Open fourth round

Second seeded Swiss fell to a four-set defeat to the Australian, who faces Novak Djokovic in the quarter-finals

Roger Federer was defeated in four sets by John Millman in the US Open fourth round. AFP

Five-time US Open champion Roger Federer suffered a shock defeat in the fourth round late on Monday night, crashing out in four sets to Australian world No 55 John Millman.

Federer, 37, looked to be in cruise control after he took the opening set and led 5-3 in the second, but the onset of errors and Millman's doggedness resulted in the 23-time grand slam champion go down 3-6, 7-5, 7-6, 7-6.

Millman's win sets up a quarter-final clash against Wimbledon champion Novak Djokovic, who was in ominous form earlier in the day to defeat Portugal's Joao Sousa 6-3, 6-4, 6-3.

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"Very happy to get this one done in straight sets," said Djokovic, who left the court for a lengthy break after the second set and left again for evaluation during a medical timeout early in the third before returning to wrap up the match in exactly two hours.

Sousa, who got past 12th-seeded Pablo Carreno Busta and No 17 Lucas Pouille to become the first Portuguese man to reach a grand slam last 16, was "not happy" at Djokovic's first lengthy absence from the court, although he acknowledged there was no rule limiting time of a comfort break.

More damaging may have been his ire at the chair umpire's refusal to allow a line call challenge in the seventh game of the final set on grounds he gestured too late. Distracted, he was broken at love in the next game and Djokovic served out the match without fuss.

"It was much more difficult than the score indicated," said Djokovic, who said he struggled with a "couple of things" during the match but that the heat "was the adversity today".

"You can't do anything but try to be tough and survive, find a way to win," he said.

Kei Nishikori, runner-up in 2014, was also pleased to get through in three sets in blazing sunshine on Louis Armstrong Stadium.

After racing through the first two sets against Germany's Philipp Kohlschreiber he dropped his serve while serving for the match at 5-4 in the third, but managed to prevail 6-3, 6-2, 7-5.

"Man, really lucky to finish in three sets," Nishikori said. "It was very hot on the court even though it doesn't look too hot it's hit me."

Nishikori will fight for a semi-final berth against Croatian Marin Cilic, who beat him in the 2014 final.

That remains Nishikori's best grand slam showing. After reaching a career-high fourth in the world in 2015 he slid down the rankings as a wrist injury sidelined him for six months, keeping him out of last year's US Open and this year's Australian Open.

Seventh-seeded Cilic, who needed eight match points in a five-set marathon against Australian teenager Alex de Minaur which spilled into Sunday morning, survived some tense moments to get past 10th-ranked Belgian David Goffin 7-6, 6-2, 6-4.

Goffin served for the first set at 5-4 before Cilic went on to win the tiebreaker. From there things got easier, Cilic saying that Goffin confided after the match he had a shoulder problem. But Cilic still needed a third match point to clinch it.

"I was thinking one match point, second match point -- I hope it's not going to the eighth one," Cilic said.