A youthful Bilbao went ahead through Fernando Llorente’s 13th-minute opener before Marcelo leveled in the 25th.
Ronaldo stroked home a pair of spot kicks in the second half and Jose Callejon added a late goal to secure the hosts a much-needed win following their midweek 2-1 home loss to Barcelona in the first leg of the Copa del Rey quarterfinals.
Ronaldo’s league-high 23 goals is one more than Messi’s total.
Barcelona hosts Madrid on Wednesday in the second leg.
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