Bromelain (BR), a protease extracted from Ananas comosus , reportedly possesses pharmacological activities including the reduction of thrombogenesis, and antihypertensive, and antimicrobial effects. This study aimed to investigate the potential effects of BR on oral cancer cells. The effect of BR on the viability of Ca9‐22 and SCC25 cells was determined using the MTT assay. These cells were also treated with different doses of BR, and Western blotting was conducted to monitor apoptosis. Finally, flow cytometry analysis was performed to identify sub‐G1 populations of oral cancer cells. After treatment, the viability of both Ca9‐22 and SCC25 cells was markedly reduced, in a dose‐dependent manner. BR induced poly (ADP‐ribose) polymerase (PARP) and lamin A/C degradation, and generated cleavage products. Flow cytometry analysis showed that BR treatment significantly increased the sub‐G1 population. Our findings therefore indicate that BR has potential as a novel, natural anticarcinogenic medicine.