Other big matches see Mubadala World Tennis Championship winner Kevin Anderson up against Kyle Edmund, while French Open champion Jelena Ostapenko also in action.
Nadal to test fitness, Stephens aims to end losing streak, and Kyrgios under pressure to deliver: Games to watch on Day 1 of Australian Open
Ahead of the opening day of action at the Australian Open on Monday, the first grand slam of the 2018 tennis season, here are some of the main matches to watch out for.
The full schedule for Monday's play on the main show courts can be found here.
Rafael Nadal (1) v Victor Estrella Burgos
12pm (UAE time), Rod Laver Arena
On paper Nadal should win this in his sleep. But he has only played once since withdrawing from the ATP Tour World Finals with a knee injury, and he lost to Richard Gasquet at the Kooyong Classic last week.
This will be interesting to see the state of Nadal's game and an early look at how probable a challenge for a second Australian Open title is for the world No 1.
Estrella Burgos is a journeyman pro at the age of 37 and the world No 81 should not trouble Nadal too much.
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Sloane Stephens (13) v Shuai Zhang
4am, Margaret Court Arena
Stephens looked to be set to fulfill her promise when she won her first grand slam title at the US Open in September.
But it has rather gone wrong for the American since as she has lost every match she has played, and was thrashed by world No 100 Camila Giorgi in Sydney last week.
Given her awful form, an early upset could be on the horizon here.
Kevin Anderson (11) v Kyle Edmund
4am, Court 3
This should be a cracking match. US Open finalist Anderson looked to be in good nick in December when he won the Mubadala World Tennis Championship without dropping a set.
The big serving South African has the game to go a long way in the tournament, but world No 50 Edmund is an interesting opponent.
In the absence of the injured Andy Murray he is the top British player in the draw and does have the ability to test Anderson here.
Jelena Ostapenko (7) v Francesca Schiavone
4am, Rod Laver Arena
Ostapenko impressed UAE fans in December with her ability to find winners from all angles during her win over Serena Williams at the Mubadala World Tennis Championship.
The Latvian had a breakout year in 2017 as she won the French Open and the test for her now is to build on that and be consistent.
Schiavone, 37, may be coming towards the end of her career, but the 2010 French Open champion can still cause a shock here if Ostapenko has an off day.
Nick Kyrgios (17) v Rogerio Dutra-Silva
Fourth match on Hisense Arena - likely to be no earlier than 9.30am
Kyrgios comes into the tournament in great form after winning the Brisbane International, and the effortless way he defeated Grigor Dimitrov in the semi-final was a reminder of just how good he can be when he is fully focused.
He has been as far as the quarter-finals in Melbourne in the past and the Australian public, who have not had a home winner in the men's singles since 1976, will expect him to progress deep into the tournament this time around.
It will be a surprise, based on Brisbane form, if he needs more than three sets to progress here.