Nishikori, in the third round for the fifth straight year, will take on the No.31 seed Laslo Djere who beat Alexei Popyrin 6-4, 7-6(4), 6-4.
There was further disappointment for the host nation as the No.31 seed Petra Martic steamrollered Kristina Mladenovic 6-2, 6-1. The Croatian’s next task could be fearsome – she faces Rome champion Karolina Pliskova, after the Czech ruthlessly dismantled Kristina Kucova 6-2, 6-2.
The French also lost Richard Gasquet, who succumbed to Juan Ignacio Londero. The Argentinian won 6-2, 3-6, 6-3, 6-4. But the home nation may yet gain revenge, as Londero will next meet 20-year-old Corentin Moutet, who earned a thrilling victory over the No.19 seed Guido Pella 6-3, 6-1, 2-6, 7-5.
In other women's results, Anastasija Sevastova defeated Mandy Minella 6-2, 6-4; next up for her is No.20 seed Elise Mertens, who demolished Diane Parry 6-1, 6-3.
Two-time roland-Garros quarter-finalist Kaia Kanepi got the better of Shuai Zhang in a see-saw encounter 6-7(4), 6-0, 7-5 and she will face Zarina Diyas - who beat Veronika Kudermetova 7-5, 6-1 - for a place in the fourth round.
Meanwhile, Carla Suarrez Navarro got past Shelby Rogers 6-1, 6-7(4), 6-3; and Polona Hercog edged past Jennifer Brady 6-3, 6-7(8), 6-4.