PHOTO: AFP
It was never-say-die Nishikori's third five-setter of the tournament, the second time he came from two sets down and his second triumph via a final set 10-point tie break, newly introduced for this year's tournament.
The 6-7 (8/10), 4-6, 7-6 (7/4), 6-4, 7-6 (10/8) win over the 23rd seeded Spaniard took a draining 5hr 5min after an opening set that alone lasted 76 minutes.
It ended on a sour note when Carreno Busta lost his head after a disputed call when leading the final tiebreak 8-5.
He failed to win another point and was booed from the Margaret Court Arena as he stormed off the court and angrily threw his kit bag towards the exit.
"I don't know what to say now. Very tough match. Very great match today," Nishikori said.
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Nishikori had already spent eight hours and 42 minutes on court in his first three matches, including a second-round clash that went the full distance to a final set tiebreak against Ivo Karlovic.
"I feel it's not enough," he joked of his total of 13hr 47min on court in the first four rounds. "Not easy of course. I try to recover well tomorrow.
"Today was the longest match I have had this week. I will try to be fresh for the next match."
Nishikori warmed up for the Australian Open by winning the title at Brisbane and has now reached the quarter-finals for the fourth time in Melbourne without ever going further.
In the first round Nishikori advanced after qualifier Kamil Majchrzak retired due to muscle cramping with the Japanese star leading 3-6, 6-7(6/7), 6-0, 6-2, 3-0 after also dropping the opening two sets.
He then beat Karlovic 6-3, 7-6 (7/6), 5-7, 5-7, 7-6 (10/7) and Joao Sousa 7-6 (7/1), 6-1, 6-2.
Nishikori's seemingly unlimited reserves of stamina have helped him recover from two sets down four times in Slams and he has a win-loss record in five-setters at the Australian Open of 7-1 and 21-6 overall.
The 2014 US Open finalist will face either top-ranked Novak Djokovic or 15th seed Daniil Medvedev, who he beat in the final in Brisbane.
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