But Djokovic, though playing more confidently than he has in recent weeks, still looked unprepared for the physical challenge of facing Thiem - a hugely fit and strong opponent who had also eliminated him from last year's French Open. Nadal hopes to make the semifinal of the Monte Carlo Masters for the fourth straight year.
The Serbian showed signs of promise as he continues his comeback from an elbow injury, but he let a one-set lead slip and Thiem fought back to claim a 6-7 (2-7) 6-2 6-3 win.
Russian Khachanov cruised past Gilles Simon 6-2, 6-2, while last year's runner-up Albert Ramos-Vinolas slumped to a 6-4, 6-2 defeat by Philipp Kohlschreiber. "I was predisposed to some risk and I was unable to play with that amount of pain". Djokovic is to play the next round against fifth-seeded Dominic Thiem of Austria to secure a place in the quarter-finals.
"It's [a] way better feeling if you go against him and know that you've beaten him already on this surface", Thiem said about his upcoming match against Nadal.More news: Kennebunkport recalls Barbara Bush as a generous, friendly neighbor
World number seven Thiem lost his way after a bright start in the first set against a resurgent Djokovic, but he recovered to punch his ticket to the last eight.
Khachanov held his own at times in the opening set, but Nadal moved through the gears and claimed his second comfortable victory of the week after his opening win over Aljaz Bedene. "I mean, I could have won the match earlier definitely, but it was great to deal with these kind of emotions again", said the 12-time Grand Slam champion. "I have to play an aggressive tennis, high intensity. I think I'm able to do that".
Third seed Alexander Zverev came through a three-set tussle with fellow German Jan-Lennard Struff on Thursday to set up a possible Monte Carlo Masters quarter-final with his brother Mischa.
Roberto Bautista Agut was not happy after dropping his serve in the second set against David Goffin and he hit a ball into the ground in frustration, unknowingly sending it into the direction of a ball boy.More news: UAE works on breaking up with Saudi Arabia, according to diplomatic leaks
Goffin, a semifinalist a year ago, next plays Grigor Dimitrov after the fourth-seeded Bulgarian beat Philipp Kohlschreiber 4-6, 6-3, 6-4.
Second seed Marin Cilic is also into the last eight, after Milos Raonic pulled out with a right knee injury before their third-round match on Thursday.
There were also round of 32 victories for Japan's Kei Nishikori after he clinched a 7-5 6-2 victory against Daniil Medvedev of Russian Federation.
The Australian open up runner up second plays rsquo & Japan;s Kei Nishikori, that overcome Andreas Seppi 6-0 2-6 6-3.More news: Stormy's sketch of harasser sparks social media frenzy of Tom Brady comparisons