Djokovic has won 26 of their previous matches while Nadal last beat the Serbian in the 2014 French Open final.
Rafael Nadal set up a semifinal with Novak Djokovic after withstanding a tough challenge from David Goffin 7-6 (3), 6-2 at the Madrid Open on Friday.
Djokovic is also looking to get back to his best after months of struggling for from and a win over Nadal could go a long way in building his confidence going into the second Grand Slam of the year in Roland Garros at the end of the month. However, after parting ways with his coaching team, the world number two has looked rejuvenated and determined to hit peak form.
"I'm not anxious about it", Nadal said.
On the women's side, defending champion Simone Halep of Romania cruised past Anastasija Sevastova of Latvia 6-2, 6-3 to reach her third Madrid Open final.More news: Miley Cyrus Releasing New Song About Liam Hemsworth 'Malibu'
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The Romanian will face France's Kristina Mladenovic or Russian Svetlana Kuznetsova in the final.
Zverev had been on a seven-match victory streak after winning his second title of the season in Munich last week.
And Cuevas landed the only break in the final game of the deciding set when Zverev fired wide to set up a semi-final against Dominic Thiem or Andy Murray's conqueror Borna Coric. He lost to Goffin in the quarterfinals in Monte Carlo, his first clay tournament of the season.
The same problem forced world number eight Nishikori, seeded sixth in Madrid, to miss the Barcelona Open last month but he is hoping to be fit for next week's Rome Masters.
"It will be a very hard match against one of the best sportsmen this sport has ever had, and to have a chance I'll have to be at my very best", Nadal said.