Prostate cancer (PCa) is the most common tumor in Europe and America. In recent years, the incidence rate of PCa has been increased in China. Castration-resistant prostate cancer (CRPC) is a serious difficulty in treatment of prostate cancer. The androgen receptor (AR) signal axis still plays an important role in the survival and progression of the tumor when PCa turns into CRPC. The new endocrine therapy is characterized by targeting AR signal axis, in which Abiraterone and Enzalutamide are the representatives. These two drugs can effectively inhibit the activity of AR signal axis, and prolong the survival of the patients. Although the new endocrine therapy drugs are safe and effective for CRPC, but the subsequent drug resistance can seriously affect the clinical efficacy. This paper reviews the progress on the mechanism of drug resistance of new endocrine therapy in recent years, in order to provide some references for solving the problem of drug resistance and guide the development of new drugs.