It was similarly easy on the women's side for top-ranked Victoria Azarenka and No. 2 seed Maria Sharapova, who won their matches in just more than an hour.
Nadal, ranked second in the world, has won his last 10 matches against fellow Spaniards, and 22 of his last 23 sets against them. Granollers, who has risen from 50th to 26th in the rankings over the past year, cracked a 212-km/h serve during the match, but he couldn't cover Nadal's quickness and touch.
Nadal served out the match in a deuce game, then drew cheers from female fans when removed his shirt and towelled off courtside before donning a warm-up jacket.
Azarenka, a 6-3, 6-1 winner over Julia Goerges, moved on to play fifth-seeded Agnieszka Radwanska, who advanced when American wild card Jamie Hampton retired with cramping in the third set trailing 3-6, 6-4, 3-0. Azarenka (20-0) and Radwanska (20-3) have the most match wins this year on the WTA Tour.
Sharapova, who lost to Azarenka in the Australian Open final, beat Roberta Vinci 6-2, 6-1, and next plays an all-Russian quarter-final against either 20th-seeded Maria Kirilenko or No. 30 Nadia Petrova, who met later Tuesday.
"I was pretty solid and I think my pace didn't allow her to come forward as much as she would have liked," Sharapova said about Vinci.
No. 3 Roger Federer, against Canadian Milos Raonic, and fourth-seeded Caroline Wozniacki played night matches at the Indian Wells Tennis Garden.
On the men's side, fifth-seeded David Ferrer lost for just the second time this year, 6-4, 6-3 to Denis Istomin of Uzbekistan. Ferrer had already won three titles this season, and was seeking his 20th match win.
Istomin set himself up for a fourth-round match against No. 9 Juan Martin del Potro, who defeated Fernando Verdasco 6-2, 7-6 (6). Verdasco failed to convert on six break points in the match.
"Verdasco is a really difficult opponent, especially in the beginning of the big tournaments," Del Potro said. "He's very, very tough, very dangerous, and I think I made a good match. I got lucky in the second set when I save five set points, and then in the tiebreak he made the double fault to give me the first match point."
Thomaz Bellucci advanced when Nikolay Davydenko withdrew because of illness. There was no immediate confirmation whether Davydenko was suffering from the same viral illness that has knocked eight players out of the two-week tournament.
Azarenka next will try to equal Serena Williams' consecutive victories streak of 21-0 to begin 2003.
"If I relax my butt a little bit, somebody's going to come and kick it," she said, laughing.
Azarenka, who has won two other titles this year, is 3-0 against Radwanska this year, with two of their matches going to three sets.
"She's someone who always comes up with something different," Azarenka said. "She's a little magician, if you can call it that."
Azarenka beat Radwanska in straight sets last month in Doha, during which Azarenka injured her ankle. She kept playing, but appeared to be in pain and was visibly distraught. Radwanska later said she "lost a lot of respect" for the 22-year-old Belarusian because her behaviour wasn't a good image for women's tennis.
"I actually never had a problem with her," Azarenka said Tuesday. "She's a great player, great girl, so nothing there is to discuss."
Hampton earned her first win against a top-20 player when she beat Jelena Jankovic in the second round and the 22-year-old from Auburn, Ala., was having her best tour-level results yet when she fell down early in the third set.
"She was really hitting the ball very well, very consistent, good serve and moving very well," Radwanska said. "I just noticed when she fell down. It's always tough, especially that you can't really have medical timeout for that. It's tough to come back."
Other winners were No. 6 Jo-Wilfried Tsonga; No. 8 Li Na; and 18th-seeded Angelique Kerber, who beat American Christina McHale in a third-set tiebreaker.