Top-seeded Gonzalez is trying to win his third consecutive Movistar Open and fifth in 10 attempts. He'll next face another Spaniard, Ruben Ramirez Hidalgo.
Sixth-seeded Acasuso, champion in 2006, could run into Gonzalez again in the semifinals. He lost only five points on serve and broke Podlipnik-Castillo five times. The Argentine will next play countryman Eduardo Schwank, who needed more than three hours to beat Paolo Lorenzi of Italy 4-6, 7-6 (3), 6-3.
Third-seeded Thomaz Bellucci of Brazil defeated Nicolas Lapentti of Ecuador 3-6, 6-1, 6-1, but fourth-seeded Pablo Cuevas of Uruguay, a two-time semifinalist, was upended by Ricardo Mello of Brazil, who won 7-6 (5), 6-3 in his season opener.
Two other seeds -- both making their debuts in Santiago -- were also eliminated.