A victory for Los Blancos' would see them extend their lead at the top of the league to four points, with just two games remaining.
Eight consecutive wins, including six clean sheets in their last seven, has seen Zinedine Zidane's side leapfrog Barcelona into the top spot, with his side now in pole position to claim the title.
If Madrid is victorious against tonight's opponents, a victory against Villarreal on Thursday night would see them crowned as champions before their last match of the season against relegation-threatened Leganes.
The opposition, Granada, who were promoted from the Segunda Division last season, have so far endured a successful season.
Since the restart, the Nazaries' has collected 12 points (W3, D3, L2), putting them just three points behind sixth-placed Getafe and one behind seventh-placed Athletic Bilbao - who they face on the last day of the season.
Despite being able to continue their early season form, where Granada was leading the league in late October, their current position of 10th would see them record their highest finish since the 1943/44 season when they finished eighth in the top tier.
With the game being hosted at the Nuevo Los Carmenes, there is an expectation that very little goals will be scored. Despite a six-goal thriller in the reverse fixture, the home side has scored just 21 times in their own stadium, and have conceded just 14 - making them one of the worst scorers, but also one of the best defensive sides in the league.
When these two sides last met, it was a battle between first and second in LaLiga, with the victors ending the day in the top spot.
Within just two minutes, it was Madrid who gained the lead, with Karim Benzema tapping home a Gareth Bale cross from a close range.
The then-home side made it two just before half-time when Federico Valverde fed in Eden Hazard for his first goal of the season. The Belgian lobbed Rui Silva to double his side's advantage.
With an hour played, Luka Modric smashed the ball in from outside the 18-yard box, making it an almost impossible task for Granada to find a way back into the game.
The away side fought back, though, with goals from Darwin Machis and Domingos Duarte causing a nervous last 10 minutes from Los Blancos'.
However, the Matagigantes' couldn't find an equalising goal, and it was instead Madrid who put the game to bed.
Alvaro Odriozola, now out on loan at Bayern Munich, crossed the ball into James Rodrguez who had a simple finish in stoppage time.
Going into the game, Granada will be without defensive midfielder Maxine Gonalons, with Alvaro Vadillo, Jesus Vallejo, Quni, Neydar Lozano, and Alex Martinez all a doubt.
Madrid will be boosted by the return of Dani Carvajal and Sergio Ramos, who both return to the squad after suspension.
Despite this, they will be without long-term absentee Nacho, as well as Marcelo, Mariano Diaz and Luka Jovic.
Granada: Silva, Diaz, Sanchez, Duarte, Neva, Eteki, Herrera, Azeez, Puertas, Dias, Soldado.
Real Madrid: Courtois, Mendy, Varane, Ramos, Carvajal, Valverde, Casemiro, Modric, Junior, Isco, Benzema.