Del Potro booked his place in the last four of the US Open with a victory over John Isner in four sets – 6-7, 6-3, 7-6, 6-2.
Nadal, meanwhile, is in action against Dominic Thiem, with the Austrian winning three of their 10 encounters although Thiem took a heavy beating in the French Open final in June.
Del Potro awaits in the semi-finals and he is looking to get his hands on the US Open title for the first time since 2009.
The Argentine lost to Nadal in five gripping sets at Wimbledon earlier in the summer and he wants to set the record straight.
And he appears to have his heart set on another clash with the world No 1.
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“If I play Rafa, it could be another big battle as the Wimbledon match was,” he said.
“Of course, I like to play always with the No 1 of the world, doesn’t matter the tournament or the conditions or the weather.
“I just have the chance to play the greatest on this sport, and it’s amazing for me.
“If I play Rafa, I would like to do the same thing that I did in Wimbledon.
“I was close to beating him. But he’s the No. 1 in the end.
“I will try to enjoy the semi-final, as well.”
When asked what he remembers about his 2009 triumph, Del Potro added: “ I couldn’t hold the trophy in that moment.
“I was so, so nervous, happy. I couldn’t talk to the fans in that moment, like, nine years ago.
“But I have my trophy at home. I like to see that trophy every single day in my home.
“I don’t know if I can get a new one, but I’m doing all my best to try to get again.”