The top seed, playing his first match after losing his first semi-final on clay for 12 years at the Rio Open last week, was given a bye into the second round, where he was rarely stretched in a 6-4 6-0 victory over Argentinian qualifier Facundo Arguello.
Nadal was broken in the opening set but the Spaniard converted five of his own eight break point opportunities and will face another Argentinian in the last eight after Federico Delbonis saw off Paolo Lorenzi of Italy 6-4 6-2.
Third seed Pablo Cuevas reached his third consecutive quarter-final on the ATP Tour after a 7-6 (7/4) 6-1 win over home hope Guido Andreozzi.
The Uruguayan world number 24 won the Brasil Open two weeks ago and was knocked out of the Rio Open in the quarter-finals by Nadal in his last tournament.
He will face former world number 10 Juan Monaco, who upset fifth seed and Argentinian compatriot Leonardo Mayer 6-4 6-4.