Barcelona's struggles in La Liga in recent weeks mean they now trail Real Madrid and the holding midfielder suspects defeat on March 23 would end their hopes
Barcelona are 4/1 with bet365 to win the 2013-14 Primera Liga
The Catalan club moved into the quarter-finals of the Champions League with a 2-0 (4-1 aggregate) win over Manchester City on Wednesday and are back in league action when they host Osasuna on Sunday, but Busquets has already set his sights on the Clasico seven days after that game.
"We have come from an adverse outcome that makes it tough to win the league, but we still have to go to the Bernabeu and fight until the end," the midfielder told Marca.
"We are four points behind and it seems we cannot fight for the title, but the game at the Bernabeu will decide everything.
"If we win, we keep fighting, but if we lose then the league will be over."
Los Blaugranas will head to the Santiago Bernabeu third in the table and four points adrift of Carlo Ancelotti's leaders, with Atletico Madrid sitting second, providing all three times win this weekend.