Defending Italian Open champion Novak Djokovic suffered a shock quarter-final elimination at the hands of Danish protege Holger Rune on Wednesday.

The 22-time Grand Slam champion fell to a 2-6 6-4 2-6 in a rain-affected contest, denying Djokovic a 10th-straight semi-final appearance on the Rome clay.

Thanks to a fiery last-16 win over British number one Cameron Norrie on Tuesday, Djokovic was competing in the Italian Open quarter-finals for the 17th year running, although he hinted at a physical glitch earlier in the week.

Clearly not 100% in the opening exchanges of their quarter-final, Djokovic was quickly broken twice as a ruthless Rune stormed into a 5-1 lead, before missing a set point on Djokovic's serve.

The 20-year-old did not dwell on that missed opportunity, though, hitting a trio of winners in game eight to take the first set, but Djokovic was not giving up the ghost.

The Serbian earned the first break of the second set for a 4-2 lead, but as the clouds began to gather, Rune stormed to a 40-0 lead on Djokovic's serve and broke back before a weather-enforced delay.

The hiatus undoubtedly came at the worst time for Rune, who lost his momentum and was subsequently broken to love by Djokovic as play resumed, seeing the defending champion force a third set.

However, Rune continued to display a vast array of sweetly-struck shots to earn the double break in the deciding set, and after Djokovic missed one chance to break back on the Dane's serve, his run in Rome was over.

"I stay humble of course. I have a lot to achieve. I think you should always be humble. I think I am, I hope so and I hope people see me this way," Rune said on the court following his triumph.

"I think I was a little less brave in the second set but after the rain delay, I managed to come out and be brave even though I lost the set. I just told myself, 'Okay, it's all right, I just have to keep going."

"I'm a huge fighter on the court and I leave everything when I play my matches. I'm super proud I was able to get the victory today. I had to fight hard and play my best tennis. Huge credit to Novak, I'm a big fan of his. He's a huge inspiration and I wish him all the best."

Rune's second successive win over Djokovic has seen him rewarded with a semi-final showdown against fellow Scandinavian Casper Ruud, who bested Argentina's Francisco Cerundolo 7-6[5] 6-4.