Matches against Sevilla have proved rich pickings for Ronaldo and it was no different on Saturday as he followed up Karim Benzema's 18th-minute opener with goals in the 26th, 46th and 59th minutes as Madrid sauntered to victory.
That took his tally of hat-tricks for the Spanish giants to an incredible 20 before he was replaced in the 63rd minute as Jose Mourinho opted to wrap his trump card in cotton wool ahead of Wednesday's visit of United in the first leg of the Champions League last-16 clash.
Granada, who stunned Mourinho's men last weekend with a 1-0 win courtesy of a Ronaldo own goal, continued where they left off against the champions on Saturday evening as they trounced Deportivo La Coruna 3-0 at the Riazor.
Carlos Marchena's own goal on the stroke of half-time set the visitors on their way and Ighalo's strike six minutes after the restart doubled their advantage.
Depor then missed a number of chances to get themselves back into the game and their night was summed up when they conceded a dubious penalty - converted by Guilherme Siqueira - in the last minute and saw Manuel Pablo sent off.
A last-gasp goal by substitute Nelson Valdez clinched a 1-0 win for Valencia against Celta Vigo at Balaidos, providing Ernesto Valverde's side with the perfect springboard ahead of Tuesday's Champions League clash with Paris St Germain.
Isco scored twice as Malaga moved back into fourth place thanks to a 2-1 win at fellow European hopefuls Levante.
Jose Barkero put the home side in front with a 27th-minute penalty, but Isco restored parity through a spot-kick in the 37th minute and then sealed the points with a neat finish just after the restart.
Finally, a stoppage-time equaliser by Pedro Geromel earned Real Mallorca a 1-1 home draw against Osasuna.
Lolo had put the visitors ahead 15 minutes from time at the Iberostar Stadium and looked to have handed Gregorio Manzano the worst possible start to his third spell in charge of Mallorca until Geromel's late intervention.
Mallorca 1-1 Osasuna
Celta Vigo 0-1 Valencia
Levante 1-2 Malaga
Real Madrid 4-1 Sevilla
Deportivo 0-3 Granada