Rafael Nadal, playing his third tournament in four weeks after a seven-month injury layoff, beat Argentina's Leondardo Mayer 6-1, 7-5 in the quarters and will now play Nicolas Almagro.
Ferrer, the top seed and three-time defending champion whose world number four ranking puts him one spot higher than Nadal, breezed past Italy's Paolo Lorenzi 6-3, 6-1 to book a semi-final clash with Fabio Fognini.
While Ferrer has won three straight titles in Acapulco, the return of Nadal to a tournament he last played in 2005 has electrified fans.
It is the third of three Latin American clay court tournaments Nadal tabbed for his comeback from a left knee injury.
He opened with a runner-up finish at Vina del Mar -- his first tournament since a surprise second-round exit at Wimbledon in June -- and followed up by lifting the title in Sao Paulo, Brazil, two weeks ago.
And he has insisted this week that he is still planning to play the upcoming hard court Masters Series events at Indian Wells and Miami, although he is playing with intermittent pain in his knee.
Ferrer went down an early break against Lorenzi but bounced back quickly and broke the Italian five times en route to the victory in 72 minutes. He next faces another Italian in Fognini, a 7-5, 6-4 winner over Colombia's Santiago Giraldo.
Nadal's next opponent Almagro, a two-time winner in Acapulco, beat Horacio Zeballos of Argentina 6-3, 6-4, firing down 10 aces in the 70-minute encounter.
Almagro's win denied Nadal the chance for revenge against Zeballos, who beat the Spanish number two seed in the final at Vina del Mar, Chile, in his first tournament back from his lengthy injury layoff.