The cup holders were well beaten in an ill-tempered match against city rivals Real Madrid last week, and will need to record a big win if they are keep hopes of retaining the trophy alive.
Atletico have not lost at home in all competitions this season and Simeone still has hope that they can pull off a sensational second-leg victory.
"Qualification will be difficult but nothing is impossible in life," the 43-year-old said on Monday.
"We have to focus on improving.
"The team fight, play, work and do not look for excuses.
"I always said I want an Atletico team that made it uncomfortable (for Real) and we are getting there."
Atletico have a dreadful home record against Real, who have won their last seven games at the Vicente Calderon.
‘Even though it was late in the game, the Arsenal fans started singing my name. It felt like the moment I announced myself as a professional footballer’: Ex-Gunners star recalls scoring first senior goal as a teenager at Highbury
'I started to drive myself crazy': Former Manchester United midfielder explains why it all went wrong for him under Erik ten Hag
