Abstract: The paper is to investigate the derivatives of echinocystic acid(EA) and their application as chemosensitizer in vitro and their mechanism. The sensitive and adriamycin resistant strains of human breast cancer cell line MCF-7 and human hepatocellular carcinoma cell line HepG-2 were cultured in vitro and the IC₅₀ of adriamycin and its test compounds were determined by MTT method and then the resistance times were calculated. Subsequently, resistant strains were co-cultured with different concentration of adriamycin and its test compounds, MTT assay was used to determine the cell viability of each group, the test compounds to calculate the reversal times of EA and its derivatives.The results show that EA and its derivatives had less cytotoxicity at low concentration, but they could significantly enhance the sensitivity of drug-resistant cells to the chemotherapeutic drug adriamycin, and the reversal times could reach more than 15 times; EA derivatives are dose-dependent; EA and its derivatives inhibit the delivery of P-gp in resistant strains, and reduce the pumping of chemotherapeutic drugs from the cells, thus enhancing the sensitivity of the chemotherapeutic drugs.In conclusion, EA and its derivatives have chemosensitization effect, and the mechanism is partly or wholly attribute to the inhibition of P-gp.