In just 91 minutes inside RLA, the top seed and defending champion made a statement behind a 6-3, 6-1, 6-2 victory over Jeremy Chardy.
Novak's US Open title defence came to a halt on Sunday when the Serb retired from his fourth-round match against Stan Wawrinka. The Swiss led, 6-4, 7-5, 2-1, when the top seed stopped due to a left shoulder injury. They were facing off for the first time since the 2016 US Open final.
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.
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.