Nishikori extended his impressive record in five-set matches to 23-6, including a 6-1 mark at the clay-court Grand Slam.
There were passages of play in some of those matches when Federer appeared to have found the secret.
"Even though I was in the main draw, I was still in the qualifying locker room".
French Open tournament director Guy Forget did not rule out playing semi-finals across three courts or moving a final to Monday if further rain delays strike on Friday.
Federer, playing his first French Open since 2015, has lost all five meetings he has had with Nadal in Paris.
In the men's quarterfinals, it'll be No. 3 Roger Federer vs.
The 2009 French Open champion struck 53 winners on Tuesday, as Wawrinka's 61 unforced errors proved costly.
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Hot on the heels of the leaders and one shot back at 8 under is Jordan Spieth , who started the day one shot off the lead. A 14 footer read perfectly well helped Shubhankar move to 4-under for the round as he went past the 12th hole.
Wawrinka had saved 22 of 27 break points in his epic last-16 victory over Stefanos Tsitsipas, including all eight in the deciding set, and he was at it again on Tuesday, making it seven from seven to move 3-1 in front in the second. And I think the last two points of the match ended up in volleys.
The Swede says Federer will gamble early in rallies. Their fourth-round match had been suspended by darkness on Sunday, with Nishikori leading two sets to one.
Nadal, 33, is into his 12th semi-final at Roland Garros and has won the tournament on all of the 11 previous occasions he has reached this stage. Add in the fact Nishikori had survived back-to-back five-set thrillers to reach the quarters, and it made things very hard for him. Rafa won 54% of his receiving points which allowed him to break Kei Nishikori's serve on 7 occasions.
The 29-year-old Nishikori managed just nine winners in total in the first two sets.
Women's fourth round: No. 3 Simona Halep beat Iga Swiatek 6-1, 6-0; No. 8 Ashleigh Barty beat Sofia Kenin 6-3, 3-6, 6-0; No. 14 Madison Keys beat Katerina Siniakova 6-2, 6-4; Amanda Anisimova beat Aliona Bolsova 6-3, 6-0.
And despite Nadal's pedigree on the red stuff, former women's world No 5 Hantuchova is backing Federer to produce what would be a shock win despite being one of the best players on the ATP Tour for 15 years.
I say unlikely with what I consider to be solid rationale.
The 37-year-old eventually won 7-6 (7-4) 4-6 7-6 (7-5) 6-4 in three hours and 17 minutes on Court Suzanne Lenglen.
The three-time major victor became the first player at Roland Garros this year to take a set off Federer, the 37-year-old converting just two of the 18 break points that came his way.