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The Spaniard took three hours and 17 minutes to obtain a 7-6 7-5 7-6 straight-sets win over his plucky Japanese opponent who, despite his refusal to back down to the top seed's dominance, was unable to land a deserved victory in a single set.
The 13-time Grand Slam winner, who has now won all six meetings with Nishikori, had not been broken previously in the tournament, but dropped four of his service games before finally ending the impressive challenge of the 24-year-old.
Nadal is trying to win the Australian Open for the second time and secure the 14th Major of his career, that would leave him equal with Pete Sampras and three behind Roger Federer's leading total of 17. The Australian Open is the only Major he hasn't won at least twice, with his only success coming in 2009.
It's the seventh time in Nadal's last seven appearances at Melbourne Park that he has advanced to the quarter-finals, although he didn't play the Australian Open last year due to a left knee injury and stomach virus.
Nadal will take on 22-year-old Bulgarian Grigor Dimitrov on Wednesday.