Hormotherapy and chemotherapy are still the most important palliative therapeutic approaches for androgen-sensitive prostate cancer (PCa). Recently, the combination of hormotherapy and chemotherapy, namely, chemohormonal therapy has aroused considerable attention. Although synergistic chemohormonal therapy can improve PCa suppression efficacy and prolong the lives of patients, it also leads to severe adverse effects, that is, hormonal tolerance caused by hormotherapy, and leukemia or neutropenia caused by chemotherapy. Therefore, alleviating the adverse effects and improving anti-PCa efficacy are the focuses of the chemohormonal therapy for future researches. In this study, the commercial androgen-deprivation therapy (ADT), polyester microsphere Enantone (ENT), and polypeptide micelles loaded with a clinical antitumor agent mitoxantrone (MTO) are employed for micro/nanocarrier-assisted chemohormonal therapy. Encouragingly, the combined chemohormonal therapy significantly boosts antitumor efficacy and ameliorates side effects in preclinical assessments. With these benefits, the micro/nanocarrier-assisted chemohormonal therapy can be incorporated as an efficient clinical strategy for PCa patients.