He is chasing a record-extending fifth Paris Masters title and advanced toward that when Damir Dzumhur retired trailing 6-1, 2-1.
"It's been a hard year for me in terms of injuries, and so I'd prefer to avoid doing anything drastic", he told the media minutes before his intended match against compatriot Fernando Verdasco who will instead face Tunisian lucky loser Malek Jaziri.
"I always believe in myself, but it was highly improbable, considering my ranking and the way I played and felt on the court".
The 37-year-old Swiss had only made a late decision to compete in Bercy after winning his 99th title in his home town Basel on Sunday but, despite a touch of raggedness, was sharp enough to outclass the Italian 6-4, 6-3 in his opening match.
Fifth-seeded Marin Cilic, the Australian Open runner-up, won his second-round match 6-3, 6-4 against Philipp Kohlschreiber of Germany.
The 10th-seeded Nishikori did not face break points in beating the seventh-seeded Anderson - the Wimbledon runner-up to Djokovic - 6-4, 6-4.
He will play Karen Khachanov after the 22-year-old bested John Isner 6-4 6-7 (9-11) 7-6 (10-8).
Later Thursday, third-seeded Roger Federer was facing Fabio Fognini. Fernando Verdasco, who reached the quarter-finals past year, produced a clinical display to defeat Frenchman Jeremy Chardy 6-4, 6-4. I checked with the doctor and the doctor said it is recommended I do not play.
The win improved the Croat's prospects of making the ATP Finals in London starting on November 11.
"I am very close to London, to securing my spot mathematically", Cilic said.
"In the next match against Novak it will be another big challenge".
Lucky loser Malek Jaziri replaced Nadal and beat Verdasco 7-6 (5), 1-6, 6-3 and next faces defending champion Jack Sock.
In a high-quality contest between two others seeking a London berth, Dominic Thiem, back in the city where he reached the French Open final, ended Borna Coric's slim hopes while boosting his own with a 6-7 (3) 6-2 7-5 win.