Ashleigh Barty and Barbora Krejcikova can stay on course for a high-class semi-final collision, while Rafael Nadal looks to continue his march to a record 21st Slam title as the Australian Open hits the quarter-final stage on Tuesday.

Home hope and world number one Barty thrilled the crowd by defeating the giant-killing Amanda Anisimova 6-4, 6-3 in the fourth round and faces another American, Jessica Pegula, in the night session on Rod Laver Arena.

French Open champion Krejcikova swept past two-time Melbourne champion Victoria Azarenka 6-2, 6-2 to set up a last-eight meeting with unseeded American Madison Keys.

Barty, the 2019 French Open and 2021 Wimbledon champion, looks in irresistible form as she chases her first Australian Open crown.

The 25-year-old comfortably dispatched the 20-year-old Anisimova, who had already accounted for defending champion Naomi Osaka and Tokyo Olympics gold medallist Belinda Bencic.

Top seed Barty, who is aiming to become Australia's first women's champion on home soil in 44 years, warned she will not make it easy for Pegula.

On course: Ashleigh Barty is aiming to become the first Australian woman in 44 years to win her home Open
On course: Ashleigh Barty is aiming to become the first Australian woman in 44 years to win her home Open AFP / William WEST

"I try to adapt my game as best as I can to try and make my opponent uncomfortable," said Barty. "And that will be no different when Jess and I play."

Pegula, who revealed last week she had been relaxing with nights at the casino, was a surprise winner over fifth seed Maria Sakkari of Greece.

"That was definitely my best match of the year," declared the 27-year-old Pegula after reaching the last eight for the second successive year.

French Open champion Krejcikova will open the day on Rod Laver Arena against Keys, who raced past Spain's eighth seed Paula Badosa 6-3, 6-1.

Keys, who won the Adelaide warm-up event, beat 2020 champion Sofia Kenin in the first round and has 10 match wins in 2022, just one short of her total for the whole of 2021.

A semi-finalist at Melbourne Park in 2015 but unseeded this year, Keys puts her revival down to a fresh perspective after struggling previously with Covid-enforced bubble life on tour.

Rafael Nadal has been pumped up during his run to the quarter-finals in Melbourne
Rafael Nadal has been pumped up during his run to the quarter-finals in Melbourne AFP / Martin KEEP

"I don't really thrive when my entire life becomes about tennis," she said.

Nadal had to survive an epic 28-minute tiebreak to seal his quarter-final berth against Canada's 14th seed Denis Shapovalov.

The Spanish great showed all his experience and tenacity to prevail 16-14 in a tiebreak, the longest of his illustrious career, before beating France's Adrian Mannarino in straight sets.

"First set was very emotional," said the 35-year-old Nadal, who won his lone Australian Open back in 2009.

A second this year would take him ahead of absent rivals Novak Djokovic and Roger Federer, who also have 20 Grand Slam titles.

The 22-year-old Shapovalov -- who caught Covid-19 before the Slam and was not even sure he would play in Melbourne -- enjoyed a routine win against an out-of-sorts world number three Alexander Zverev.

"After coming out of quarantine and playing the ATP Cup, I had a little bit of doubt, wasn't ready to play the first match and worked my way through the tournament," said Shapovalov, who said he suffered aches and pains while recovering from the virus.

"I wasn't practising that much, to be honest, and just trying to prepare the body as best as possible," he said.

Veteran Frenchman Gael Monfils meets big-serving Italian Matteo Berrettini in the last quarter-final on Tuesday and warned the seventh seed: "I'm not quite finished yet".

The 35-year-old 17th seed Monfils is yet to drop a set in Melbourne while Berrettini sent down 28 aces in sweeping past Spain's Pablo Carreno Busta.

"He's feeling good, I'm feeling good," said Berrettini. "It's going to be a fight."