Title favourite Daniil Medvedev and Nick Kyrgios will square off on Thursday in a blockbuster second-round encounter that could play a big part in shaping the destiny of this year's Australian Open men's singles title.

Andy Murray will be back on the rowdy John Cain Arena after an epic five-set win on Tuesday, while other men to watch will be fourth-ranked Stefanos Tsitsipas and fifth seed Andrey Rublev.

Russia's Daniil Medvedev faces a formidable obstacle in Nick Kyrgios in their second-round encounter on Thursday Russia's Daniil Medvedev faces a formidable obstacle in Nick Kyrgios in their second-round encounter on Thursday Photo: AFP / Paul Crock

In the women's draw, third seed Garbine Muguruza of Spain faces French veteran Alize Cornet in second-round action, while Britain's Emma Raducanu will look to repeat her resurgent form that saw her power past Sloane Stephens.

But all eyes will be on world number two Medvedev -- the de facto top seed after Novak Djokovic was thrown out of Australia -- and the maverick, volatile Kyrgios, who won both the pair's previous meetings in 2019.

Nick Kyrgios pulled out his full bag of tricks in the first round against Liam Broady, including a trademark 'tweener' Nick Kyrgios pulled out his full bag of tricks in the first round against Liam Broady, including a trademark 'tweener' Photo: AFP / William WEST

With Djokovic out and Roger Federer absent because of injury, the draw has opened up for the 25-year-old US Open champion Medvedev -- but first he has to get past Australian showman Kyrgios and the raucous antics of his legion of home fans.

"It's definitely going to be not easy against the crowd. He's going to try to pump himself up, like, he likes to play big names," said Medvedev, who will take on Kyrgios in the prime-time evening match on centre court, Rod Laver Arena.

"I think our last match was so long ago... that it's really tough to count it."

Turning back the clock: Andy Murray won his first match at the Australian Open since 2017 Turning back the clock: Andy Murray won his first match at the Australian Open since 2017 Photo: AFP / William WEST

Kyrgios said he was looking forward to locking horns again with Medvedev, who he beat in Rome and Washington three years ago.

"It's going to be a hell of an experience for me. You know, he's probably 'the' best player in the world at the moment," said Kyrgios.

Britain's Emma Raducanu can set up a potential clash with her childhood idol Simona Halep Britain's Emma Raducanu can set up a potential clash with her childhood idol Simona Halep Photo: AFP / Brandon MALONE

"I'm excited for that moment. That's why I play the game."

But he will have to do it away from the cauldron of his favourite court, the John Cain Arena, which the 115th-ranked Australian called "the Kyrgios Court".

That venue will instead belong to Murray for the evening, after the Briton turned back the clock in typically combative style for his first win at the Australian Open since 2017 on Tuesday. He faces qualifier Taro Daniel of Japan.

Greek fourth seed Tsitsipas continues his bid for a maiden Grand Slam title against 88th-ranked Argentine Sebastian Baez, while Russian fifth seed Rublev comes up against Ricardas Berankis of Lithuania, the world number 93.

Women's US Open champion Raducanu has been rewarded for her highly entertaining rollercoaster 6-0, 2-6, 6-1 victory over Stephens with a prime evening slot on Margaret Court Arena against Danka Kovinic of Montenegro.

A win for Raducanu, who has Romanian heritage, could set up a potential third-round clash against former world number one Simona Halep, who the British teenager idolised when she was growing up.

The two will clash for the first time if they both win, with the Romanian two-time Grand Slam champion Halep following Kyrgios and Medvedev on to court for a late-night clash against Beatriz Haddad Maia of Brazil.

Anett Kontaveit had a breakout 2021 season and the Estonian sixth seed continues her tilt at a first Grand Slam title against Denmark's Clara Tauson.

Struggling world number two Aryna Sabalenka managed to scrape into the second round in three sets despite 12 double faults. The Belarusian faces China's Wang Xinyu for a place in the last 32.