Novak Djokovic got rid of the young Italian Lorenzo Musetti with difficulty in five sets, after the latter's abandonment (6-7 [7], 6-7 [2]), 6-1, 6-0, 4- 0).
Argentina's Diego Schwartzmann, a semi-finalist last year, also qualified for the quarter-finals.
Novak Djokovic qualified for the quarter-finals at Roland Garros on Monday, but it was far from a walk in the park.
The world No. 1 was jostled by the young Italian prospect Lorenzo Musetti (76th), who won the first two sets before giving up in the fifth when he was behind 6-7 (7/9), 6- 7 (2/7), 6-1, 6-0, 4-0.
In the next round, the Serbian, finalist last year, will face Matteo Berrettini (9th), another Italian.
Argentinian Diego Schwartzman (10th) also climbed to the quarter-finals, without losing a single set after dismissing German Jan-Lennard Struff (42nd) 7-6 (11/9), 6-4, 7-5.
Coco Gauff in quarterfinals at 17
In the women's draw, rising star Coco Gauff qualified for the first time in her career in the quarterfinals of the Paris tournament.
The 17-year-old American dispatched the Tunisian Ons Jabeur (26th) 6-3, 6-1 in just 53 minutes.
In the next round, she will face the Czech Barbora Krejcikova (33rd) who will also play, at 25, her first quarter of the Grand Slam.
Monday's round of 16 results:
Men's singles (round of 16):
Matteo Berrettini (ITA / N.9) beats Roger Federer (SUI / N.8) (forfeit)
Diego Schwartzman (ARG / N.10) beats Jan-Lennard Struff (GER) 7-6 (11/9), 6-4, 7-5
Ladies' singles (round of 16):
Cori Gauff (USA / N.24) beats Ons Jabeur (TUN / N.25) 6-3, 6-1
Barbora Krejcíková (CZE) beats Sloane Stephens (USA) 6-2, 6-0