Nishikori was trailing 6-1 5-1 when he decided to follow the advice of his coach Michael Chang, who could be heard saying "Don't push it, it's not worth it."
The Japanese fifth seed, who swallowed a pill given by the trainer at the previous change of ends, shook his head at the umpire to indicate he could no longer continue before going up to Cilic to shake hands.
While the Croatian ninth seed looked forward to a quarter-final with seven-times champion Roger Federer, a dejected Nishikori was left to reflect on how injury scuppered his Wimbledon dreams for the second year in a row.
"It was too much pain I could not really compete today. Every point I played it got worse. I did not want to but I had to retire," Nishikori, who withdrew from last year's tournament with a calf strain, told reporters.
News that makes sense
Your trusted source for staying up-to-date with the world around you. Get free daily news updates and analysis, straight to your inbox.
Cilic's serving was on fire during the first set as he blasted down 12 aces, including four in the first game, and dropped only two points on serve.
He won 26 out of 33 points contested as Nishikori surrendered the set in only 16 minutes.
The 2014 U.S. Open champion, who beat his Japanese rival in Flushing Meadows to win his only grand slam title, could not keep up the same intensity in the second set as Nishikori broke back to level at 1-1.
But from then on Nishikori failed to win a game and, after dropping serve for the third time in the set, with a double fault, he could not hide his despair.
While Chang, the 1989 French Open champion, indicated with his hands to 'cut it', Nishikori covered his eyes before burying his head under a towel as he slumped into his chair.
When the trainer came on court and handed a pill to Nishikori, it was clear that Asia's number one player was struggling and one game later it was all over as muted applause greeted Cilic's passage into the last eight.
"When he started to hit some serves, I noticed that he's not hitting them at all," Cilic said after recording only his fourth win in 12 meetings with Nishikori.
"Then in the first couple of games I was trying to see where he's not comfortable at all to try to play that obviously.
"It was definitely a tough situation for him."
(Reporting by Pritha Sarkar, editing by John Stonestreet)
