Holders Barcelona will take on Athletic Bilbao in the last 16 of the Copa del Rey while Real Madrid have been paired against Sevilla in two mouthwatering clashes.
There is also guaranteed to be a second division team in the quarter-finals after Alcorcon and Cordoba were drawn against each other, but it is the two heavyweight showdowns that catch the attention.
The tie between Barca and Athletic is a repeat of the 2012 and 2015 finals - both won by the Catalan giants - and again pits together the two most successful clubs in the tournament's history.
Barca, who have reached the final five times in the last six years, have won the Copa del Rey 28 times while Athletic have lifted the trophy 23 times - although not since 1984.
Luis Enrique's men also beat Athletic in last year's quarter-finals before going on to defeat Sevilla in the final.
The other eye-catching tie from Friday's draw sees 19-time winners Real take on Sevilla - throwing the reigning Champions League winners against the three-time Europa League holders.
Real director Emilio Butragueno, whose side host the first leg at the Bernabeu, said on his club's website: "It doesn't matter if the first game is at home or away. The team will return to work next week and we need to prepare well for the first leg and get a good result.
"We know that it's difficult to play in Sevilla in front of very enthusiastic fans."
The full draw for the last 16 is: Las Palmas v Atletico Madrid, Alcorcon v Cordoba, Athletic Bilbao v Barcelona, Real Madrid v Sevilla, Real Sociedad v Villarreal, Deportivo La Coruna v Alaves, Valencia v Celta Vigo and Osasuna v Eibar.
The ties will be played in the first two weeks of January.