Los Blancos are the underdogs to progress to the final eight due to a 2-1 loss in the first leg at the Bernabeu.
Zinedine Zidane's side have since won La Liga, though, and have been in excellent form since returning to the field following the lockdown period.
Here, Sports Mole looks at how the reigning Spanish champions could line up when they take to the field against Pep Guardiola's side at the Etihad Stadium.
Madrid will be without club captain Sergio Ramos for the second leg, with the central defender picking up a red card in the reverse match at the Bernabeu, meaning that Eder Militao could be handed a spot at the back alongside Raphael Varane.
Ferland Mendy should get the nod over Marcelo at left-back, while Luka Modric and Toni Kroos have both been in excellent form since the lockdown period, and it would not be a surprise to see the pair line up alongside Casemiro in the middle of the park, leaving Federico Valverde on the bench.
Zidane has decisions to make further forward; Karim Benzema is a certain starter at the tip of the attack, but it remains to be seen which two players join him in the final third of the field.
Hazard has only scored once for Los Blancos this term and was not involved in his side's last league game of the season against Leganes. The former Chelsea attacker has been in full training ahead of this contest, though, and is expected to be handed the chance to make his mark against a team that he knows well.