South Africa’s top-ranked player, who entered the year’s first Grand Slam as the No 14 seed, defeated Frenchman Richard Gasquet 6-4 7-6 7-6 in their third-round clash.
Nadal, a 14-time Grand Slam champion, swept past unfancied Israeli Dudi Sela in the third round with a convincing 6-1 6-0 7-5 win.
“Anderson is a big player with a big serve,” Nadal said in his post-match interview. “He’s very dangerous and he will be a very tough opponent for me.”
Earlier on Friday, Raven Klaasen, a finalist last year with former partner Eric Butorac, was eliminated in the second round of the men’s doubles.
Klaasen and India’s Leander Paes won the first set but ultimately went down 6-2 4-6 1-6 against Italian duo Simone Boleli and Fabio Fognini.