Nishikori was cruising through the second set up a break at 5-3. Harrison held serve, then broke Nishikori in a lengthy 10th game. Harrison saved four match points before Nishikori hit a backhand into the net, giving Harrison his break and tying the set at 5-all.
Nishikori, the world's seventh-ranked player, broke back in the next game and then served out the match to move to the third round. He'll face Kazakhstan's Mikhail Kukushkin, who upset fifth-seeded Denis Kudla 6-1, 7-5 earlier Wednesday.
"I think he started playing a little better that game," Nishikori said of Harrison in the 10th game. "I kind of had a double fault (up 40-30), something, easy mistakes. I should've closed out. But happy to finish the last two games."
Throughout the evening match, Nishikori countered Harrison's strong serve with a strategy of running Harrison from side to side along the baseline with an occasional drop shot to keep Harrison off balance. Harrison has won only once in 25 matches against the world's top 10 players.
Nishikori and Kukushkin faced each other in the Round of 16 at Brisbane in January, with Nishikori defeating Kukushkin 6-3, 6-4 on a hard surface similar to the one at this week's tournament.
"It was two sets, but it was a tough one," Nishikori said. "He's always (a) tough player. Especially with this slow condition, it's going to be many long rallies. I'm going to have to stay tough."
Kukushkin, ranked 93rd in the world, got off to a quick start in the opening set against Kudla, an American who entered the tournament with a career-best ranking of 59th. The second set was more competitive, but Kudla was unable to overtake Kukushkin.