Novak continued his good run on Parisian clay as he defeated Albert Ramos-Vinolas 7-6 (5), 6-1, 6-3 to reach the last 8.
The second seed moved into the French Open R4 for the 11th time with a five-set win over Diego Schwartzman.
Novak cruised into the French Open third round with straight sets win over Joao Sousa (6-1, 6-4, 6-3).
The reigning title holder started his Roland Garros campaign with a 6-3, 6-4, 6-2 win over Marcel Granollers.
The world no.2 and two-time champion lost to no.4 seed Rafael Nadal 2-6, 4-6 in one hour and 38 minutes.
Kei’s withdrawal sends the defending champion into last 4 where he will face Rafael Nadal (ESP, 4).
Novak recorded a 6-4, 7-5 victory over Feliciano Lopez in one hour and 33 minutes on Thursday.
Nole goes on to play Feliciano Lopez (ESP, H2H 8-1) in the last 16 on Thursday.
The 2011 and 2016 champion will open campaign at La Caja Mágica in R2 against Spanish wild card Nicolas Almagro (ATP #76).
Djokovic earned his 300th ATP World Tour Masters 1000 victory, beating no.31 seed Juan Martin del Potro 7-5, 4-6, 6-1.