The former world number one needed only 78 minutes to prevail over Brazilian Joao Souza, ranked 101st in the world 6-3, 6-4.
Nadal advanced to the quarter-finals which will be played Friday.
“It was an important victory for me,” Nadal said. “the conditions are very difficult. The court is very fast, the ball too.”
Asked about his injured left knee, he replied: “Today I think it was acceptable, normal. Let’s hope it will be the same tomorrow. The important things is that it (the knee) does not hurt.”
Wednesday, the Spanish star withdrew from a scheduled doubles match he was to have played with Argentina’s David Nalbandian against Argentine Horacio Zeballos and Austrian Oliver Marach, citing “knee overuse”.
Nadal, currently ranked number five in the world, only returned to the tour in Chile last week after a seven-month injury absence.
The 11-time grand slam champion, who lost both the singles and doubles finals Sunday at his comeback event in Vina del Mar, Chile, is the top seed at this week’s event here.
The $455,775 Brazil Open is part of the Latin American clay court circuit, along with the Vina del Mar and the Mexico Open in Acapulco where Nadal plans to play later this month.