Prostate cancer is the most frequently diagnosed cancer for men in Western countries. Prostate cancer is caused by multi-factorial processes, and epigenetic alterations are important key factors for tumorigenesis. Epidemiological studies provide evidence that nutritional factors, especially consumption of soy isoflavones, have considerable effects on decreasing morbidity and mortality of prostate cancer. The modulatory effects of soy phytoestrogens on epigenetic regulation mechanisms gain importance due to their role on providing further opportunity for prostate cancer prevention. phytoestrogens have a remarkable potential on the regulation of DNA methylation patterns in prostate cancer cells. Phytoestrogens may enhance the reactivation of methylation-silenced genes by inhibition of DNA methyltransferases (DNMT) activity or increasing protein levels of histone acetyltransferase 1, which leads to histone 3 lysine 9 acetylation. Recently, we analyzed the regulatory effects of genistein and daidzein on DNA methylation by using methyl-DNA immunoprecipitation method coupled with Human DNA Methylation Microarrays (MeDIP-chip) in LNCaP and DU-145 cells. We observed that methylation profiles of 58 genes were altered with genistein and daidzein treatments in prostate cancer cells. In addition, the methylation frequencies of MAD1-like 1 (MAD1L1), TNF receptor-associated factor 7 (TRAF7), lysine (K)-specific demethylase 4B (KDM4B), and human telomerase reverse transcriptase (hTERT) genes were remarkably modified. In conclusion, soy phytoestrogens can regulate gene activity by altering DNA methylation and/or histone modification patterns. Since epigenetic mechanisms are reversible processes, the role of soy phytoestrogens on epigenetic mechanisms gains importance, correspondingly, epigenetics-driven novel therapeutic candidates warrant further consideration in future “omics” studies of prostate cancer.