World number two Murray blasted past eighth seeded Czech Tomas Berdych 6-3 6-2 in their quarter-final while Nadal had a harder task on home clay in seeing off Portugal's Joao Sousa 6-0 4-6 6-3.
The roof had to be closed on both matches at the 'Caja Magica' due to rain.
"We know each other very well," said Nadal, who has won his last two meetings with Murray with the most recent victory coming in the Monte Carlo semis three weeks ago.
"It's a question of playing my best, and if I am playing my best I hope to have my chances. If not, it will be almost impossible."
Murray took 76 minutes to beat Berdych, winning 92 percent of his first service points and with no break points against him.
"It was different conditions playing under the roof," he said. "I've only played maybe three or four indoor clay matches in my life."
Nadal dominated the first set, with Sousa taking 37 minutes to win a game when he made it 1-1 in the second before a 10-minute rain delay as the roof was closed.
With Real Madrid's Portuguese striker Cristiano Ronaldo watching, Sousa saved three break points in the sixth game and then broke Nadal in the 10th to take the set.
"The ball was a little bit heavier," said Nadal. "I missed a few good opportunities. I had to suffer. I had to fight back and look for a solution. I managed to find a solution and solve it."
(Reporting by Alan Baldwin, editing by Toby Davis)
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