Real Madrid will take on Clasico rivals Barcelona in the Copa del Rey semifinals while Athletic Bilbao will face Osasuna following Monday's draw.
The reigning Spanish champions will host Barca before visiting the Camp Nou, in the only round of Spain's national knockout competition held over two legs.
"It's a huge game, not only for the Copa del Rey, it's a big game across the world," Barcelona's sporting director Jordi Cruyff said in reaction to the draw held near Madrid.
Cruyff said his players had already moved on from their 3-1 win against Real Madrid in this month's Spanish Super Cup final in Saudi Arabia.
"We start from zero and it will be a wonderful battle," he added.
Athletic Bilbao -- who have reached the Copa del Rey semi-finals for four seasons running -- gained their place in the final four with a 3-1 victory over Valencia in the last round.
Their opponents Osasuna knocked out Sevilla in the quarter-finals with a 2-1 win after extra time.
The first legs will be played on February 28 and March 1, while the return fixtures will be held between April 4 and 6.
Seville's La Cartuja stadium is due to host the final on May 6.