Colombian ace Muriel scored and set up countryman Duvan Zapata for another as Atalanta warmed up for the Spanish champions with a 4-2 win over Napoli to move up to fifth in Serie A at the weekend.
"Muriel is extraordinary, not only for the assist and the goal," said coach Gian Piero Gasperini after the forward scored in a ninth consecutive Serie A appearances as a starter.
"This year he has shown extraordinary mental, physical and athletic form, he has made a terrific leap in quality also in terms of consistency."
The match against 13-time European champions Real will be the biggest game ever played by the Italian team whose only major trophy was the 1963 Coppa Italia.
"It's a unique opportunity," said Muriel.
"If Atalanta play like against Napoli, conceding little and creating a lot, it will be very difficult for them too."