Earlier, Argentina's Juan Martin del Potro had a less troubled win over Uruguay's Pablo Cuevas 7-6, 6-4, saving all three break points he faced during the 98-minute match.
He will now face big-hitting American Isner, who thrashed Leonardo Mayer 6-0 6-3 to book his place in the last-eight of the tournament.
What time does Nadal play Isner?But still I didn't have the control of the match for nearly all the time. More news: Canada Cancels Plans to Build Pipelines
Nadal needed all his experience to keep Pouille at bay in the decider and the match looked to be heading for another tiebreak before he pounced to break Pouille's serve for the first time to go 6-5 up.
Second seed Alexander Zverev served seven aces as he beat Britain's Kyle Edmund 6-3 7-6 (3) in the day's last match and will meet Italy's Fabio Fognini in the next round.
"I thought in the beginning we both played pretty well, from the baseline especially", said Zverev.More news: Walmart Buys East Williamsburg Package Delivery Service
Cirstea follows fellow Romanian Simona Halep into the quarter-finals after the second seed sent Maria Sharapova packing on Wednesday. The U.S. Open quarterfinalist continued his good run to end the season by beating seventh-seed Tomas Berdych 1-6, 6-4, 6-1.
In the women's draw, former world No. 1 and fourth seed Karolina Pliskova became the latest high-profile casualty, going out in the third round to unseeded Sorana Cirstea. She will play Latvia's Jelena Ostapenko, the Roland Garros champion, after China's top player Peng Shuai retired with a knee injury at 3-0 down in the first set.More news: The UK's manufacturing sector was weaker than expected in September