Japan’s Kei Nishikori has ground out a five-set upset win over second seed Andy Murray to reach the US Open semi-finals.

Nishikori, who became the first Asian man to reach a grand slam final when he finished runner-up at the 2014 US Open, scored a 1-6 6-4 4-6 6-1 7-5 victory on Wednesday.

He broke the Scotsman in the 11th game of the fifth set with a brilliant reflex volley and served out to complete the comeback triumph.

“It was so exciting on the court but I tried to stay calm. It was really tough,” said Nishikori after reaching only his second Slam semi-final.

“He’s a great returner, there were lots of up and downs. I didn’t start well.”

Murray looked to be in control at two sets to one ahead and carving out a break point in the third game of the fourth set, before the umpire ordered the point to be replayed as a result of malfunctioning public address system in Arthur Ashe stadium.

Andy Murray loses his cool. Photo: Getty.

Murray lost his composure and the next five games as Nishikori levelled at two sets all.

The upset ended a stellar run by Murray that had taken him to seven successive finals, including victories at Wimbledon, the Rio Olympics, Queen’s Club and Rome.

The sixth-seeded Nishikori will meet either double grand slam winner Stan Wawrinka or 2009 US Open champion Juan Martin del Potro in the last four at Flushing Meadows.

— with AAP