The temperamental talent produced some of his best tennis to beat the Russian 16th seed 6-2 7-6 (7-5) 6-7 (8-6) 6-7 (9-7) 7-6 (10-8) in the longest match of his career - a four hour and 26 minute classic on Saturday night.

It sets up the most anticipated match of the 2020 Open - a clash with bitter rival Rafael Nadal.

But this one will go down for the ages, Kyrgios blowing two match points across the third and fourth set and also battling a bloody hand, mini-meltdown and a superb comeback from his opponent to eventually get the job done.

"It was definitely one of the craziest matches I've ever been a part of," he said.

"It was insane. Had a match point in the third, a match point in the fourth. Then 8-7 down, I had all the thoughts.

"I thought I was going to lose. I was thinking about everything. I was thinking about the media if I lost, everything. It was crazy.

"It was one of the best wins of my career I think."

Kyrgios started off in electrifying fashion, overcoming an early glute complaint and medical time out to race through the first set.

The second was tighter as Khachanov warmed into the match following his four hour and 34 minute second-round epic against Mikael Ymer.

It stayed on serve before Kyrgios overcame a mini-break in the tiebreak to claim the set.

With a 4-2 advantage to Kyrgios in the third, the match looked done, but, much like in his second round encounter with Gilles Simon, he handed it back with the finish line in sight.

Kyrgios had one match point on the Khachanov serve but he couldn't claim it, with the Russian then stealing the set on his opponent's serve.

In a tight fourth set Kyrgios lost his cool when given a time warning on serve - the Canberran bitterly complaining about a bleeding hand he'd sustained falling over the previous point.

"Are you stupid? Can you not see? Why did I get a time violation, my hand is bleeding," he told umpire Renaud Lichtenstein.

Kyrgios later explained that his hand was squirting blood and he didn't want the ballboy to have to touch his towel.

"Then the umpire just had no idea what was going on apparently. My hand is usually brown. It was covered in blood. Something wrong there," he said.

After Khachanov fended off another match point he went on to claim the set in a a third tiebreak, setting up the decider.

While Kyrgios stayed on the edge, there was no tipping point and the clash stayed on serve until the match tiebreak which Kyrgios won 10-8 before collapsing to the ground.

Australian Associated Press