1025 GMT November 22, 2019
Serbia's Djokovic, 31, was leading 6-1, 4-1 when Nishikori quit with a thigh problem, BBC Sport reported.
The top seed will face Lucas Pouille in Friday's semifinal, after the Frenchman defeated Milos Raonic.
Spanish second seed Rafael Nadal and Greece's talented 20-year-old Stefanos Tsitsipas will contest the other semifinal today.
Djokovic has not lost to Nishikori in their past 15 meetings, stretching back to the Japanese's victory in their 2014 US Open semifinal.
"I love to battle especially against Kei, we have played so many matches in our careers," Djokovic said.
"I hope he can recover and it is not something very serious that will take too long.
"I am sorry for everyone not having a full match tonight but thank you for showing up."
Nishikori, 29, had spent almost 14 hours on court in his four matches on route to the quarters – over four hours more than Djokovic.
The four-time Australian Open quarterfinalist needed more than five hours to beat Spain's Pablo Carreno Busta in their last-16 match on Monday.
"Before the match I was OK, I wasn't fresh but thought I was going to be OK," Nishikori said.
"After the third or fourth game I was serving, I felt heavy in my right leg and couldn't bend my knees or jump up.
"So I decided to stop. I couldn't beat anyone with just one leg.
"I'm sure it comes from my past matches, especially the last match. I was moving a lot and wasting energy."
Serena Williams said she "did not choke" after missing four match points as Czech seventh seed Karolina Pliskova won the final six games to win a dramatic Australian Open quarterfinal.
The 37-year-old American, going for a record-equaling 24th Grand Slam singles title, led 5-1 in the decider but lost 6-4, 4-6, 7-5 in Melbourne.
"I think she just played lights out on match points," Williams said.
"I took my chances," said Pliskova who won on her third match point.
Former world number one Pliskova will meet Japan's fourth seed Naomi Osaka in the last four today with eighth seed Petra Kvitova taking on unseeded American Danielle Collins in the other semifinal.
Williams, seeded 16th, played down an ankle injury which she suffered during the rally on her first match point when serving at 5-1, 40-30.
The seven-time Australian Open champion did not win another point on serve after the incident.
"She was hitting lines and went crazy. She played unbelievable on match points," Williams said.
"It was nothing to do with my ankle. Obviously I made some mistakes but she played really well."
Williams' inability to seal victory means a highly anticipated rematch of her controversial US Open final defeat by 21-year-old Osaka must wait.
Like Osaka, Pliskova will be playing in the Australian Open semifinals for the first time and is one victory from appearing in her second Grand Slam final, following defeat by Germany's Angelique Kerber in the 2016 US Open.
Pliskova had led by a set and a break at 3-2 before the momentum swung to Williams and victory appeared a formality after she won nine games out of 10 and set up a match point.
But the momentum then swung back again to Pliskova in a chaotic encounter.
"I was almost in the locker room but now stand here as the winner," she said.
"My mind was in the locker room at 5-1 down but I was still here. I was too passive and mentally down but she got a little bit shaky.
"Naomi Osaka is dangerous but there is nobody more dangerous than Serena."