Tsitsipas takes on Kyrgios in tasty Wimbledon clash
Fourth seed Tsitsipas is the only other top-10 player left in Nadal's side of the draw, while fiery Australian Kyrgios is a match for anybody on his day.
Tsitsipas's confidence is sky-high after he clinched his first grass-court title in Mallorca last week and he now has an 8-2 record on the surface this season.
The Greek player is facing a man he has beaten just once in four matches.
Kyrgios, who came out on top when the two players met in Halle last month, has been making waves at Wimbledon on and off the court.
His opening win over Britain's Paul Jubb was marred by his admission that he spat in the direction of fans, whom he accused of being disrespectful, and he also took aim at officials.
The 27-year-old, who was fined $10,000 over Tuesday's incidents, has been also in a testy mood in his post-match press conferences but he remains bullish.
"I just feel like I'm comfortable in my own skin," the 40th-ranked player said after his straight-sets win over Filip Krajinovic.
"Some people love to just tear me down. It's just not possible anymore."
Tsitsipas, who reached the fourth round in 2018, said he was "thrilled" to be facing Kyrgios, who beat Nadal on his way to the quarter-finals in 2014.
"I respect him a lot, on the court, what he's trying to do," he said. "Although he has been a little controversial in the past, I think he's playing good tennis."
Second seed Nadal, chasing a calendar Grand Slam, is aware he has not yet hit the heights at the All England Club after two scrappy performances so far.
"I didn't play much on grass in three years," the 22-time Grand Slam winner said following his four-set win against Ricardas Berankis.
"It gives me the chance to keep going, so very happy for that.
"I need to improve. The fourth set was much better.... I have to keep working, be humble, even when things are not going well."
Badosa v Kvitova
In the women's tournament, world number one Iga Swiatek aims for a 38th straight win against unseeded Alize Cornet after she was taken to three sets by Lesley Pattinama Kerkhove in the previous round.
The Polish top seed, asked if her winning streak gave her confidence, said it not enter her mind while she was playing matches.
"I'm just trying to figure out what to do better and how to kind of come back," she said. "So it doesn't really matter for me."
Fourth seed Paula Badosa takes on two-time former champion Petra Kvitova in one of the most eye-catching ties of round three.
British wild card Katie Boulter, who downed last year's beaten finalist Karolina Pliskova in the second round, plays France's Harmony Tan, who sent Serena Williams packing in her opener.