Nadal was broken twice in the third set -- getting a time violation from chair umpire Evanthia Asderaki in one of them.
Sixth-seeded Roger Federer equaled Jimmy Connors' record by reaching his 41st Grand Slam quarterfinal with a 6-3, 7-5, 6-4 win over Jo-Wilfried Tsonga in the fourth round. It was also the 11th straight year the Swiss star has reached the quarters at Melbourne Park.
Nadal is trying to win the Australian Open for the second time -- his first title came in 2009 -- and secure the 14th major of his career, equal with Pete Sampras and three behind Federer's leading total of 17. The Australian Open is the only major he hasn't won at least twice.
It's the seventh time in Nadal's last seven appearances at Melbourne Park that he's advanced to the quarterfinals. He didn't play the Australian Open last year due to a left knee injury and stomach virus.
Nadal will play 22-year-old Bulgarian Grigor Dimitrov on Wednesday. Dimitrov advanced to his first Grand Slam quarterfinal in his 14th attempt after beating No. 11 Roberto Bautista Agut 6-3, 3-6, 6-2, 6-4 on Monday. He clinched the match by breaking Bautista Agut's serve for the fourth time.
Federer and Tsonga met twice in the quarterfinals of Grand Slams last year, with the Swiss player winning their match at the Australian Open and the Frenchman prevailing at the French Open.
Federer next faces fourth-seeded Andy Murray in the quarterfinals. He has won just four of his last 14 matches against top-10 players, including Monday's victory over 10th-seeded Tsonga.
Wimbledon champ Murray ended lucky loser Stephane Robert's unexpected run at the Australian Open with a 6-1, 6-2, 6-7 (6), 6-2 win over the Frenchman in a fourth-round match Monday. Murray wasted two match points on serve in the 10th game of the third set and two more in the tiebreaker before Robert rallied to send it to a fourth.
The three-time Australian Open finalist has faced only one player ranked inside the top 100 -- No. 26 Feliciano Lopez, who he beat in the third round -- in three of his four matches this tournament.
The Associated Press contributed to this report.