The Spaniard, who had his right knee strapped during his third-round win on Thursday, said he wanted to try and be ready to face Filip Krajinovic in the last eight but that "it wasn't possible to play".
He did not say if he would be fit to play at the World Tour Finals in London later this month.
"Yesterday (Thursday), the pain was very strong but it was not the moment to stop," Nadal told a press conference.
"I had treatment last night to try and be able to play today... But unfortunately it was impossible for me to return to the court in the same condition as last night. It is a sad day for me."
Nadal has fought back this year from a series of knee problems, winning the French and US Open titles.
But he allayed fears this would lead to another lengthy spell on the sidelines, after injury-plagued campaigns saw him fail to reach a Grand Slam semi-final in 2015 and 2016.
"I had a long year, a lot of matches. I pushed the body," Nadal added.
"We are at the end of the season. It's normal that these kind of things happen. The knee is always, you know, bothering a little bit, but sometimes it's worse, and now is a little bit worse."
But the 16-time Grand Slam champion then ended his bid for a first Paris Masters title, a serious blow for a tournament which is already missing the likes of Roger Federer, Andy Murray and Stan Wawrinka.
If Nadal pulls out of the Tour Finals, it would leave Federer as the only member of the 'Big Four' in the year- ending event.
"I'm going to do my treatment, do my best to be playing in London, but I cannot talk about that now because (it) is a day that is tough enough for me to pull out from here," he said.
World number 77 Krajinovic, who had never been past the second round of a Masters tournament before, now progresses to his first ATP semi-final of the season against either Juan Martin del Potro or John Isner on Saturday.
"I did not expect this at all, I was ready to play but then I heard he had pulled out," said the Serb.
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