Abstract In recent years, antimicrobial peptides (AMP) have received increasing attention not only as antimicrobial agents, but also as potential drugs applied in cancer therapy. Through searching for databases, our laboratory screened to have active AMP, SEQ34 and SEQ11. Here we examined the action of both SEQ34 and SEQ11 on human colorectal cancer cell lines, SW480. Cell lines were cultured in presence of either SEQ34 and SEQ11, the viability of these cells were significantly reduced with increases in AMP concentration. To determine the apoptotic effects of SEQ34 and SEQ11 on cell lines, using flow cytometry (FCM) to detect apoptosis by sub-G1 population of DNA and annexin V-FITC/ propidium iodide (PI) staining of the cells. The results show that AMP treatment can inhibit SW480 cell proliferation and induce apoptosis. To explore the mechanism that induces apoptosis of SW480 cells, western blot was used to measure protein expression levels of apoptosis. The result of western blotting analysis indicated SW480 treated with AMP showed the activation of caspase 3, 6 and 9 but not caspase 7. These results suggest that the SEQ34 and SEQ11 induce apoptosis by way of the intrinsic pathway.