Kei Nishikori has yet to taste victory over Rafael Nadal on clay
Nishikori, who lost to Nadal in straight sets - 6-3, 6-2 in the final of the Monte Carlo Masters on Sunday, has lifted the Barcelona Open twice in 2014 and 2015.
Nadal captured his 31st Masters title in the process at Monte Carlo, further underlining his dominance on clay.
The Japanese ace, who sat out the event last year with a wrist injury, has only won two of their 12 meetings.
The pair could meet in the third round providing Nadal beats Roberto Carballes Baena and Nishikori defeats Guillermo Garcia-Lopez.