The Japanese, who reached the US Open final in 2014, has moved seamlessly into the last eight for the second year running, but faces the toughest test of all against Federer on Centre Court.
Nishikori is at least fit and firing, having often struggled with injuries in key matches in the past, and will have to be at his very best to stop the eight-time champion racking up a century of wins at SW19.
Federer, who has barely broken sweat on his way to the quarters, is wary, though.
“I think it’s going to be tough,” he said. “He’s getting into quarters with a lot of energy.
“I remember some of the slams recently he arrived into the later stages of slams with maybe some tough matches going into it. So far it’s been really easy for him.
“I think he’s ready. I’m a big fan of his game.”
Nishikori knows the size of the task in front of him.
“I’m sure that I have to play good tennis to beat Roger, because he’s the best player on the grass,” he said.
“I think he seems to be playing good this week, so I’m happy to be playing Roger now because I think I’m in good shape now.”
That is the standout tie of the quarter-finals of a men’s draw that has again highlighted just how far ahead Federer, Novak Djokovic and Rafael Nadal are from the rest.
All three men have dropped just one set so far and will be big favourites to progress.
Nadal is up against 2017 semi-finalist Sam Querrey, who is hoping to blow the Spaniard away with his serve.
“It’s his least favourite place of the slams and he’s been in the final five times. And he’s been rolling through guys,” he said.
“It’s going to be tough. I’m going to have to take my chances when I get them.”
Djokovic is up against David Goffin, who is enjoying his best ever run at Wimbledon and ranks his opponent as the best of the big three.
“Novak is playing so well in grand slams,” he said. “When he’s playing his best tennis, he is the world No 1 and is probably the best.”
Quarter-final debutants Robert Bautista Agut and Guido Pella face off in the remaining tie.