Natural cantharidin is derived from Mylabris phalerata. As one of the traditional Chinese insects medicine, cantharidin has certain therapeutic effects on solid tumor(e.g. digestive tract tumors), stubborn ringworm, scrofula, warts, alopecia areata and facial nerve palsy. Western basic research shows that cantharidin plays an important role in biological processes of tumor cells in vitro, such as apoptosis and autophagy, and has significant anti-tumor activity. The natural cantharidin has obvious toxicity and side effects. The direct use of related drugs not only has a strong irritating effect on skin and mucosa, but also significantly causes damage to some major organ(e.g. liver, kidney, stomach), thus limiting its wide application in clinic. Recent studies have shown that artificial cantharidin chemical derivatives (norcantharidin, cantharidin amide, sodium cantharidate, etc.) can significantly reduce side effects and retain part of the natural cantharidin’s biological functions, which is expected to become a kind of potentially effective drug for tumor and other diseases. This review aims to describe the mechanism and application prospects of cantharidin and its derivatives in cancer therapy.