The Portugal forward, 30, will surpass Raul’s record of 323 goals if he scores a hat-trick at the Bernabeu.
Ronaldo, who has netted eight times in his last two matches, has reached 321 goals in fewer than half of the games played by former Spain striker Raul.
“He is the best in the world,” said Madrid manager Rafael Benitez.
Wales forward Gareth Bale is not available for the visit of mid-table Granada, having been ruled out for two to three weeks with a calf injury.
Bale, 26, limped out of Real’s 4-0 Champions League win over Shakhtar Donetsk in midweek.
Benitez is also without Spain centre-back Sergio Ramos, Colombia midfielder James Rodriguez and Brazil right-back Danilo through injury.
Madrid have scored 15 goals in their last three matches, but trail arch-rivals Barcelona in La Liga by two points after drawing their opening game.