This review aims to elucidate the epigenetic regulation of SETD2 and EZH2 in prostate cancer, focusing on their molecular mechanisms of action, involvement in metastasis, effects on histone modification, and impact on gene expression regulation to promote or inhibit prostate cancer metastasis, to offer a basis for prostate cancer diagnosis and treatment, as well as for the research and development of novel drugs. This evidence concerns the gene SETD2 and Familial prostate cancer.