Roddick, the top seed, defeated Nishikori 6-2, 6-4. Nishikori, at age 18, became the youngest winner on the ATP circuit in 10 years when he defeated James Blake to capture last week's tournament in Delray Beach, Fla.
Nishikori, born and raised in Japan but training in Florida, added a win over Diego Hartfield in the first round of this event before running into Roddick.
Roddick will play either Mardy Fish or Denis Gremelmayr in the quarterfinals.
Blake, seeded second, also reached the quarterfinals Thursday with a 6-3, 6-4 decision over Jesse Levin. Hao Lu was a 6-4, 6-4 winner over Wayne Odesnik and John Isner surprised No. 3 seed Tommy Haas 4-6, 7-6 (8-6), 6-3.
Blake's opponent in the quarterfinals will be Robby Ginepri.
Celebrity Families of 2014 [PHOTOS]