Real have enjoyed much the better of this fixture in recent years, recording seven wins and two draws in the last nine meetings.
Carlo Ancelotti's side hold a four point lead at the top of the table, although that could be cut to just one by the time they kick off against Villarreal, with second-placed Barcelona visiting Granada 24 hours earlier.
Since a 4-0 thrashing at fierce rivals Atletico Madrid three weeks ago, Real have responded well with league wins over Deportivo La Coruna and Elche sandwiching victory at Schalke in the UEFA Champions League.
All three games were won 2-0, as was the reverse fixture with Villarreal back in September, courtesy of goals from Luka Modric and Cristiano Ronaldo.
Modric (thigh) remains an injury concern, as do Sami Khedira (thigh), Fabio Coentrao (calf), and James Rodriguez (fractured metatarsal).
Sergio Ramos (hamstring) is also a doubt, but the defender has been singing his coach's praises this week.
"Ancelotti was a player himself, he knows all about players who come in from outside the club and he understands the problems they might have," Ramos told FIFA's official website.
"He notices how a player settles in, whether he makes an effort to open up to his team-mates or not. He's a coach who takes you aside, talks to you and makes everything as smooth as possible, both on a professional and personal level.
"That's the key to success, which is why he's a truly great coach."
Real have a superb home league record, having won nine on the spin at the Bernabeu, scoring 32 goals in the process.
They also have the benefit of a full week's rest since their win at Elche, whereas Villarreal were in action on Thursday against Salzburg in the Europa League.
Marcelino's men returned from Austria with a 3-1 success, which booked their passage to the last 16 of the competition following a 2-1 victory in the home leg, and they will now face Liga rivals Sevilla in the next round.
Luciano Vietto scored twice on Thursday, taking his tally for the season to 18 in all competitions, and Real will have to be wary of the Argentinian if they are not to concede ground on their title rivals.
Villarreal have not won away from home in the league in their last four matches, but their previous victory before that run came at champions Atletico - so Marcelino's side have experience of upsetting the odds on the road.
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