Hewitt, who received a bye in the first round, easily defeated Christophe Rochus of Belgium, 6-2, 6-1.
Next up for Hewitt will be American Todd Martin, who eliminated ninth seed Xavier Milasse of Belgium, 7-5, 6-3.
Hewitt has won three tournaments this year and can be the first player to win this event three straight times since John McEnroe from 1979-81.
Second-seeded Tim Henman of Britain also advanced Thursday with a 6-1, 6-2 win over American Robby Ginepri.
Henman moves on to a quarterfinal encounter with Hyng-Taik Lee of Korea, who topped American Vincent Spadea, 6-4, 6-3.
Fifth seed Sjeng Schalken of the Netherlands also defeated an American opponent on Thursday, outlasting 12th seed Jan-Michael Gambill, 7-6 (7-4), 1-6, 6-4.
Wayne Arthurs of Australia earned the right to play Schalken in the quarterfinals by virtue of a 6-4, 3-6, 7-5 win over American Michael Russell.
Wayne Ferreira of South Africa, the 10th seed, outlasted hard-serving Mark Philippoussis of Australia, 7-6 (7-5), 4-6, 7-6 (7-5) in a marathon match to reach the quarterfinals.
Raemon Sluiter of the Netherlands advanced to face Ferreira when Karol Kucera of Slovakia retired due to an injury while trailing 3-1.
Swim Week Miami Beach 2014 [PHOTOS]