The 16-time Grand Slam champion Nadal saw off the young Russian Karen Khachanov 6-3, 6-3 to set up a clash with Isner in Beijing.
They are joined in the last eight by second seed Alexander Zverev, the rising German star who beat Italy’s Fabio Fognini 6-4, 6-2 in the final match of the day.
The in-form Isner, the American sixth seed, is renowned for his booming service game and Nadal expects to come under a barrage today.
Isner was impressive in blasting his way past Argentina’s Leonardo Mayer 6-0, 6-3 and Nadal said: “Tomorrow will be a tough one against Isner, he’s playing unbelievably well.
“I saw him today, he played so aggressive, having a lot of success, hitting a lot of winners, returning very well.
“Everybody knows that he serves huge and it is so difficult to break him.
“But if you add that he is playing very well now from the baseline, he is one of the toughest opponents you can meet.”
Nadal, 31, the top seed and coming off the back of a third US Open title, saved two match points against Frenchman Lucas Pouille in his opener in Beijing.
But he was always in control on the outside hard courts against Khachanov, 21, breaking him in the fourth game of the first set on the way to a routine victory.
Andrey Rublev ensured a Russian presence in the men’s draw as he sprang a surprise in fighting back to oust seventh seed Tomas Berdych 1-6, 6-4, 6-1.
Wozniacki out
In the women’s, a heavyweight clash pitched two-time Wimbledon champion Petra Kvitova against Denmark’s former number one Caroline Wozniacki.
The Czech Kvitova stormed through the first set 6-1 and although Wozniacki was better in the second set, Kvitova broke her for 6-4 and will play compatriot Barbora Strycova in the quarters.
Another former world number one, fourth seed Karolina Pliskova, became another high-profile casualty, going out to unseeded Sorana Cirstea.
Cirstea follows fellow Romanian Simona Halep into the quarter-finals after the second seed sent Maria Sharapova packing on Wednesday.
Cirstea, ranked 44 in the world, stunned the Czech Pliskova 6-1, 7-5 to reach the last eight.
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.
The 31-year-old Peng said she had been having injections to ease the pain and her right knee was heavily strapped, but she could not play on.
“The doctor suggested I should take a period of rest and get it treated, but I can only rest after the season, that’s the plan,” said Peng, ranked 25 in the world.
World number one Garbine Muguruza and reigning champion Agnieszka Radwanska are both out, leaving world number two Halep as the favourite in the Chinese capital.
Halep plays Daria Kasatkina of Russia and France’s Caroline Garcia takes on Elina Svitolina of Ukraine in the quarter-finals.
Garcia is in red-hot form after winning the Wuhan Open on Saturday.
