Real host the Catalans at the Bernabeu on Saturday knowing victory will put them within one point of their arch rivals with four matches left, while Barca can take a huge step towards a first league triumph in three years.
"Winning the Clasico is the key," former Real midfielder Zinedine Zidane said on Real's website.
"Beating Barcelona would send a signal and create a great chance to be league champions," he added. "If Real Madrid win everything will be different and the league can have a new frontrunner."
Barca's 2-0 victory at the Nou Camp in December, Juande Ramos's league debut as Real coach, put them 12 points clear, but the champions then went on a stunning run of 17 wins and one draw in 18 matches to haul themselves into contention.
Real's elimination from the Champions League and the King's Cup has allowed them to concentrate fully on the Primera Liga, while Pep Guardiola's side are still alive in all three competitions.
The Clasico is sandwiched between Barcelona's two-legged semi-final against Chelsea in Europe's top club competition.
Barca stuttered in February and early March when they drew with Real Betis and then lost to city rivals Espanyol and Atletico Madrid.
Their 2-2 draw at Valencia last weekend, when Real came from a goal down to win 4-2 at third-placed Sevilla, injected new life into the title race.
"If I was a Barcelona player I would be very scared to see a team like Madrid breathing down my neck," Real defender Marcelo told Thursday's As newspaper.
HUMILIATING DEFEAT
Barca visit the Bernabeu for the first time since last season's humiliating 4-1 defeat when they had to applaud Real on to the pitch in the traditional tribute to the newly-crowned league champions.
Argentina forward Lionel Messi, who scored Barca's second goal in the 2-0 win in December, said there was no desire among the players to avenge that loss.
"Let's hope we can win in Madrid and that will be a big step toward winning the title," he said at a media event in the Catalan capital on Wednesday.
"If we win, we'll be able to go to Chelsea (next week) feeling more relaxed," he added. "We are a very close-knit team and are all very motivated to win a title for Barca after two years without one."
Both coaches have problems with injuries and suspensions.
Barcelona defender Rafael Marquez is out for the season after damaging a knee in the 0-0 home draw with Chelsea on Tuesday, and Real defender Pepe has been banned for 10 matches following his sending off against Getafe on April 21.
Real will also be without midfielder Guti, who has an ankle injury, and it is unclear whether winger Arjen Robben and midfielder Wesley Sneijder will recover from muscle strains in time to feature.
