A traditional Chinese medicine cantharidin which was previously found to be effective on colorectal cancer cells was translated into nanoparticles for drug delivery to reduce its side effects and enhance its drug efficacy. By further introducing the folate targeting ligands to the nanoparticles, targeting delivery of cantharidin to colorectal cancer is realized. Cantharidin loaded nanoparticles can increase the cytotoxicity of cantharidin on the folate over-expressed HT-29 cells; moreover, introducing folate to the nanoparticles can further increase its efficacy, while this obvious enhancement cannot be found on the MCF-7 cells with lower folate receptors.