Defending champion Novak Djokovic made the set win Thursday.
The top-ranked Serbian star eased past 12th-seeded Spaniard Nicolas Almagro 6-3, 6-4 in 82 minutes on the hardcourts at Indian Wells Tennis Garden and will face American John Isner in the semifinals.
Djokovic tallied three service breaks and improved to 3-0 lifetime against the clay-court specialist Almagro. He has lost only one match this season.
Later, the 11th-seeded Isner fired 11 aces and bounced back from a poor second set to down 13th-seeded Gilles Simon 6-3, 1-6, 7-5 in under two hours.
Djokovic also captured Indian Wells in 2008 and was the 2007 runner-up here to Nadal.
Friday's marquee quarterfinal matches will pit a second-seeded Nadal against former Wimbledon runner-up David Nalbandian and third-seeded Roger Federer against ninth-seeded former U.S. Open champ Juan Martin del Potro.
Nadal is a two-time Indian Wells winner, while his fellow former No. 1 Federer captured the event three straight times from 2004-06.
The 2012 Indian Wells titlist will collect $1 million.