Khachanov, currently ranked 50th in the world, entered the tournament unseeded at a Grand Slam for the first time since Wimbledon in 2018.
But he is in his third Grand Slam semi-final after making it to the last four at the 2022 US Open and the 2023 Australian Open.
He will face either top-seeded Alexander Zverev or Dutch veteran Botic van de Zandschulp for a place in the final.
Khachanov's run to the quarters had featured wins over third-seeded Canadian Felix Auger-Aliassime and rising US talent Learner Tien, seeded 14th.
In Blockx, he faced an opponent who was already battling injuries coming in.
"I really saw that he was suffering all over his body," Khachanov said.
Blockx, the first Belgian man to reach the US Open quarters, said he was on the verge of retiring with a rib injury in his fourth-round win over Francisco Cerundolo.
On Wednesday, he had medical timeouts for treatment of his foot and for apparent lower back pain that hindered him throughout.
US Open 2026
The US Open is the fourth and final Grand Slam of the tennis season, running from August 30th to September 13th. It is a hard-court tournament held at Flushing Meadows in New York City. Follow the links below for more information!
All you need to know | Men's singles draw | Women's singles draw | Latest US Open news