The majority of patients with prostate cancer (PCa) receiving androgen ablation therapy will relapse castration-resistant prostate cancer (CRPC) within 1-3 years. Docetaxel is a FDA-approved chemotherapeutic drug for CRPC, however, PCa patient receiving docetaxel develop drug-resistant phenotype after a few months. Caffeic acid phenethyl ester (CAPE) is the main component for honey bee propolis. We previously showed that CAPE can suppresses growth of PCa tumors. In this study, we explored if CAPE can suppress docetaxel-resistant PCa cells. We observed that CAPE dose-dependently suppressed proliferation of docetaxel-resistant PC-3 cells, as well as growth of this docetaxel-resistant PC-3 xenograt in nude mice. We found that CAPE treatment promoted apoptosis-related proteins and thus induced apoptosis in docetaxel-resistant PC-3 cells. In conclusion, CAPE is an potential treatment for docetaxel-resistant PCa.