Nadal dispatched the big-serving American 6-4 7-6 to move into the semi-finals in Beijing.
There he will meet Grigor Dimitrov, who beat Roberto Bautista Agut earlier today.
But it was a stunning shot in the second-set tie-break which will be remembered most from Nadal’s victory.
Isner sent down a typical rocket serve to open the breaker which Nadal got a racket to.
Isner then approached the net, looking to close the point down early with his huge wing-span.
But the Spaniard had other ideas, running on to a backhand deep in the court before putting up a lob.
At 6ft 11ins, Isner is the hardest man to lob on the ATP tour.
But Nadal weighted the shot to perfect, dipping over a helpless Isner and landing just inside the line.
Nadal went on to win the tie-break 7-0.