Barcelona will start their defence of the Copa Del Rey trophy against Segunda B side Hercules, while Real Madrid will take on Cultural Leonesa.
Luis Enrique's side will take on the Alicante-based side who they have previously beaten in all four of their previous ties, while Los Blancos take on La Leonesa 56 years after their first and only previous meeting, where Madrid triumphed 9-0.
Barca may have some knowledge of Hercules, who lost to the Catalan's B side 3-1 earlier in the season, while Zinedine Zidane's Madrid will be mindful of last season's embarrassing exit to Cadiz due to the playing of the suspended Denis Cherysev.
Last year's beaten finalists Sevilla will take on SD Formentera – the first team to reach the competition's fourth round from the fourth tier in six seasons – while Atletico Madrid will take on CD Guijuelo from the Salamanca province.
There will be an Andalucian derby between Segunda side Cordoba and Malaga, while Racing Santander – former regulars of the latter stages of the competition – will take on Athletic Bilbao and there are four all-LaLiga ties.
All first legs will be played 30th November, with the return legs on 21st December.
Copa Del Rey fourth round draw:
Alcorcon v Espanyol
Cordoba v Malaga
Cultural Leonesa v Real Madrid
Formentera v Sevilla
Gimnastic v Alaves
Granada v Osasuna
Guijuelo v Atletico Madrid
Hercules v Barcelona
Huesca v Las Palmas
Leganes v Valencia
Racing Santander v Athletic Club Bilbao
Real Betis v Deportivo La Coruna
Real Valladolid v Real Sociedad
Sporting Gijon v Eibar
UCAM Murcia v Celta Vigo
Villarreal v Toledo