The world No. 2 Djokovic crashed out of the ATP Tour event Thursday night after a 7-6 (11/9), 7-5 upset loss to sixth seeded Australian Nick Kyrgios in the first ever ATP Tour meeting between the two.
Djokovic, who was back in action this week for the first time since his shock second-round exit at the Australian Open in January, looked rusty in the one hour, 47 minute quarter-final match.
Djokovic fell in the Aussie Open to Uzbekistan's Denis Istomin, then didn't play again until this week. He managed only one win, against Slovakia's Martin Klizan, before losing to Kyrgios, who will meet big-serving American Sam Querrey for a place in the final.
Nadal bounced back from a break down in both sets to defeat Nishioka 7-6 (7/2), 6-3.
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The second-seeded Spaniard, a two-time winner in Acapulco, hammered five aces and won 81 percent of his first-serve points in the battle between the two lefthanders.
World No. 6 Nadal also kept his Acapulco unbeaten streak alive, having won 13 straight matches, and moved to 26-0 in sets in the ATP Tour event.
Nadal advanced to a semi-final meeting with Marin Cilic. Nadal has won three of four career meetings with the Croatian.
"I am excited about playing this match," Nadal said. "He is one of the best players in the world."
Nadal easily won the opening set tiebreaker by taking the first five points and then two out of the next four. He closed out the first set with a blistering cross-court forehand that froze Nishioka in his tracks.
Nishioka was his own worst enemy at times as the 21-year-old qualifier had no aces, made four double faults and won just 50 percent of his second-serve points.
In the eighth game of the first set, Nishioka was up 40-15 and, despite having three challenges on the board, he failed to challenge a Nadal forehand that was ruled in but appeared to have sailed wide.
Johnson pulled out of his scheduled quarter-final on the hardcourts with a right ankle injury he said he sustained in his victory over Ernesto Escobedo on Wednesday.