Real Madrid are "obliged" to beat Barcelona on Saturday to maintain any hope of retaining La Liga in an El Clasico clash handed extra intrigue by the political cloud overshadowing "the biggest game in world football".
Barca could face an even more hostile atmosphere than normal in the capital in the wake of regional elections in Catalonia.
Three parties favouring independence for the prosperous region from Spain retained an absolute majority in the Catalan parliament on Thursday.
On the field, Madrid are the more needy side with the European champions trailing the league leaders by a mammoth 11 points at the top of La Liga albeit with a game in hand.
"It will be a massive game," said Real captain Ramos. "It is the biggest game in the world.
"We are obliged to win more than ever for the situation we are in to try to keep ourselves in the fight for La Liga."
For the first time an El Clasico will kick-off at lunchtime as La Liga seeks more attention from Asian viewers with a potential audience of 650 million around the world tuning in to see Cristiano Ronaldo and Lionel Messi go head-to-head once more.
And Ronaldo could be paired with Karim Benzema and Gareth Bale for the first time this season.
Real's 'BBC' front three haven't played a single minute of action together, largely due to a series of injury problems for Bale.
However, the Welshman returned to play his part in the Club World Cup success with the semi-final winner over Al Jazira.
Ronaldo is also "100 percent" fit to play according to coach Zinedine Zidane despite the Portuguese returning to training with the rest of his teammates for the first time this week on Friday.
"He is 100 percent, he trained today and that is all that interests me," said Zidane, who unlike Ramos has tried to play down suggestions Madrid must win to remain in the title race.
Barca boss Ernesto Valverde believes the spectacle on the field will not be affected by the reception the Catalan giants receive.
Valverde's men also visited Madrid in October to face Atletico Madrid without problems amid heightened political tension following violent clashes in a banned independence referendum called by separatists.
"The atmosphere tomorrow will be good, I have no doubt about that," said Valverde.
"We went to play at Atletico Madrid close to October 1 when there was a lot of talk about the reception we would get and I think as a football man it is one of the best atmospheres I have seen. There was a good feeling between the teams, the fans and I expect tomorrow will be the same."
Madrid were the last side to beat Barca and in some style with a 5-1 aggregate thrashing in the Spanish Super Cup back in August.
But, since then, the Catalans have bounced back under Valverde's guidance to go 24 games unbeaten in all competitions.
To recover from Neymar's departure to Paris Saint-Germain for a world record fee, Barca have become ever more reliant on the brilliance of Messi and the Argentine has responded with 18 goals already this season.
"It will be important for us to win this game for what it means," said Messi as he picked up his award for being the top scorer in La Liga last season this week.
"A game against Madrid is special, it is at their place and we would take a significant advantage over them if we win."