In his first appearance at a Grand Slam since last year's Wimbledon, Nishikori comfortably overcame Maxime Janvier in straight sets during his first round match.
The Japanese star has stated that his aim is just to reach the second week but he will be quietly confident after some promising showings on clay in the lead up to Roland-Garros, most notably a run to the final of the Monte-Carlo Masters where he lost to Rafael Nadal.
Nishikori has previous against Paire at the French Open, defeating him in four sets back in 2013 at the third round stage.
Paire's first round match resulted in a four-set win over Roberto Carballes Baena but it was an erratic performance with the extravagant Frenchman registering over 70 unforced errors.
He will be aiming to reach the third round of his home Grand Slam for the second time in his career after reaching that stage in both 2013 and 2015.
Paire has managed to get the better of Nishikori in two of their five career meetings but neither of those victories came on clay courts.
The Philippe Chatrier crowd will get behind the entertaining Paire and that will no doubt give the Frenchman a boost as he takes on Nishikori, but it is difficult to see him having enough in his locker to overcome the talented Japanese player, who looked the more assured of the two in their respective first round wins.
Nishikori looks to be on the up after the injury problems he has suffered with his wrist, and is favoured to see this match out in straight sets.