Objective To explore the dynamic changes in monoamine oxidase A (MAOA) and forkhead box A1 ( FOXA1) levels during neuroendocrine differentiation (NED) in prostate cancer, providing new strategies for the treatment of neuroendocrine prostate cancer. Methods Cell models and mouse transplantation models of NED were established through long-term sustained induction with enzalutamide(ENZ). Dynamic expression of MAOA and FOXA1 in NED was detected by Western Blot and Real-time PCR. GEO database data were selected to analyze the dynamic trends in MAOA and FOXA1 levels in multiple NED models. We constructed a mouse transplantation model of human prostate cancer cell lines and analyzed the dynamic expression of MAOA and FOXA1 in the in vivo NED model by immunohistochemistry. MAOA expression was disrupted with lentiviral transfection, and the impact on FOXA1 was detected. Results Both MAOA and FOXA1 concentrations showed dynamic characteristics, increasing and then decreasing during the NED process. Knockdown of MAOA in prostate cancer cells led to decreased expression of FOXA1. This MAOA may play different roles at different stages of NED by acting through FOXA1. Conclusions Both MAOA and FOXA1 levels showed increasing, then decreasing, trends during NED. The expression of MAOA affected the level of FOXA1, and MAOA/FOXA1 may play a dynamic regulatory role in the NED process.