With the La Liga champions trailing their fierce rivals by 11 points in the top flight, Los Blancos captain Ramos said this weekend's fixture is a must-win game for the hosts, per Juancar Baena of Marca:
"It will be a great match. There are no words to describe the Clasico.
"It is totally different, and the most important game in the world.
"We are obliged to win now more than ever due to the situation we find ourselves in, in order to remain in the fight for La Liga."
Zinedine Zidane's Real have endured a difficult first half of the season and sit fourth in La Liga having lost twice and drawn four times in 15 matches.
Barca, meanwhile, remain unbeaten and sit atop the standings by six points from second-placed Atletico Madrid.
They have played one more game than Real but took advantage of the Madrid giants missing a league fixture due to their participation in the FIFA Club World Cup by beating Deportivo La Coruna 4-0 on Sunday to stretch the gap between the two sides ahead of El Clasico.
And that has piled even more pressure on Real.
Despite the game in hand, if Zidane's side lose on Saturday and drop 14 points behind Barca, their chances of successfully defending the title will be all but over.
However, should they win to move back within eight points—and five if they win their game in hand—they will be back in the championship conversation.
Real can take confidence from the fact they beat Barca twice before the league season began in both legs of the Spanish Super Cup.
They also have Cristiano Ronaldo back in fine form having netted eight times in his last seven appearances in all competitions.
But Barca are high on confidence having not lost since the second leg of the Super Cup—an unbeaten run stretching to 24 games in all competitions—while Luis Suarez has also returned to goalscoring form recently.
As noted by Ramos, it is set to be a huge occasion and a match Real cannot afford to lose.