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Nick Kyrgios is into the Mexico Open semi-finals with a tough three-set win over Stan Wawrinka, but John Millman has lost a tiebreak marathon to John Isner.

Nick Kyrgios has defied a hand injury and cramp to overcome three-time major winner Stan Wawrinka in three tough sets and reach the semi-finals of the Mexico Open in Acapulco.

In an encounter lasting more than two-and-a-half hours, Kyrgios won 7-5 6-7 (3-7) 6-4, setting up a semi-final showdown with American third seed John Isner.

In a later marathon, Isner beat another Australian and eighth seed John Millman 7-6 (7-2) 6-7 (4-7) 7-6 (7-4) in three hours and six minutes.

For Kyrgios, it was a second-straight victory over a top-liner. He had saved three match points before beating world No.2 and top seed Rafael Nadal in the previous round.

The Australian battled cramp during the closing stages of Thursday night's match against Wawrinka, but hung tough to claim the win despite the crowd clearly favouring the Swiss.

"I actually play better when the crowd is against me and giving me a bit of stink," the 23-year-old said.

"I love it. It gets me going."

The night did not begin well for the hard-hitting Kyrgios, who slipped while thumping a backhand in the match's opening game, leaving him with a cut on his right hand that needed medical attention.

Leg cramps, which also required a visit from the trainers, followed in the deciding set but nothing could derail Kyrgios, who won his final service game to love.

"In the first game, I just tripped over. I'm not the smoothest mover on tour and I tripped over and grazed my hand," he said.

"And the cramping was tough toward the end."

Earlier, fellow Australian Alex De Minaur, seeded fifth, lost 6-4 6-4 to German world No.3 Alexander Zverev.

Zverev's semi-final opponent will be Britain's Cameron Norrie, who beat American Mackenzie McDonald in the quarters.