The objective of this study was to investigate the role of epithelial cell adhesion molecule (EpCAM) in the genesis and the progress of prostate cancer, especially of castration-resistant prostate cancer. Protein expression of EpCAM in ten pairs of prostate cancer tissues and normal adjacent tissues, plus three cell lines, was examined. Short hairpin RNA (shRNA) interference technique was employed to silence the expression of EpCAM in prostate cancer cell LNCaP and construct a stable transfected cell line. In vitro assay was conducted to analyze the effect of EpCAM expression on the expressions of Androgen receptor (AR), Prostate specific antigen (PSA), and cellular proliferation and invasion. EpCAM was found significantly expressed higher in prostate cancer tissues than in normal adjacent tissues. In three cell lines (DU-145, PC-3, and LNCaP), the expression of EpCAM in LNCaP, androgen-dependent prostate cancer cells, was significantly higher than that in the other two. As EpCAM was silenced in LNCaP, the expression levels of AR and PSA obviously descended, and cellular abilities of proliferation and invasion were obviously inhibited.The overexpression of EpCAM has correlation with the genesis of prostate cancer, especially androgen-dependent prostate cancer. As the expression of AR is facilitated, prostate cancer cells' abilities to proliferate and invade are consequently enhanced.