Tito Vilanova's men have a 15-point advantage over Blancos in La Liga, and the Spain international will not settle for anything other than a win on Wednesday.
"We're coming into the clasico in fine form. A good result will be beating Madrid, not drawing," the 24-year-old told reporters.
"It'll be a balanced game even if there are some players missing. We need to focus on it from our own perspective. Who’s knocked out won’t be decided at the Bernabeu."
Busquets also praised team-mate Lionel Messi, who scored four goals during their 5-1 win over Osasuna and became the youngest player ever to score 200 Liga goals.
He added: "I don’t think he needs any special motivation. That’s the way he is and he wants to improve everyday, and he does!
"That’s why he’s the best in the world and really makes such a great difference."
Barca's clash with Madrid kicks off at 21:00 CET.