Abstract: Objective Cervical cancer is the fourth most common cancer in women (behind breast, lung and bowel). Cervical cancer threatens seriously the health of women and the quality of life. China is one of the high-risk areas of cervical cancer. Cantharidin, in the form of the dried body of the Chinese blister beetles Mylabris phalerata or M. cichorii, displays certain antitumor activity and induces apoptosis in many types of tumor cells. This study aims to explore the effect of cantharidin on the apoptosis, migration and invasion in Hela cervical cancer cells. Methods Cell viability was detected by CCK-8. Flow cytometry was used to analyze the apoptosis of Hela cells. Migration was tested by wound healing assay. Transwell was performed to measured invasion. The expression of P38, P-P38, P-MAPKAPK and P-Hsp27 was detected by western blot. Results The low concentration (<20 μM) of cantharidin has no obvious effect on cell viability of Hela cells, and the viability of Hela cells was above 80% after the treatment with low concentration (< 20 μM) of cantharidin. The high concentration (>20 μM) of cantharidin reduced the viability of Hela cells and the viability of Hela cells was under 80% after the treatment with high concentration (>20 μM) of cantharidin. Compared with the control group, the apoptosis in 5 μM cantharidin groups were obviously increased (P<0.05). Apoptosis in 10 μM cantharidin groups were remarkably increased (all P<0.01). Apoptosis in 20 μM cantharidin groups were significantly increased (P<0.001). After the administration with cantharidin, the migration and invasion of Hela cells in cantharidin (5, 10 μM) groups were obviously decreased (P<0.05) and the migration and invasion of Hela cells in 20 μM cantharidin group were remarkably decreased (P<0.01). Compared with the control group, the rate of P-P38/P38 and expression of P-MAPKAPK and P-Hsp27 in 5 μM cantharidin group were obviously alleviated (all P<0.05). The rate of P-P38/P38 and expression of P-MAPKAPK and P-Hsp27 in 10 μM cantharidin group were remarkably alleviated (all P<0.01). The rate of P-P38/P38 and expression of P-MAPKAPK and P-Hsp27 in 20 μM cantharidin group were significantly alleviated (all P<0.001). Conclusion Cantharidin can elevate the apoptosis and reduces migration and invasion of Hela cells by suppressing MAPK signal pathway.