Castration‐resistant prostate cancer (CRPC) and its treatment are challenging issues in prostate cancer management. Here, we report that miR‐663 is upregulated in CRPC tissues. Overexpression of miR‐663 in prostate LNCaP cells promotes cell proliferation and invasion, neuroendocrine differentiation, and reduction in dihydrotestosterone‐induced upregulation of prostate‐specific antigen expression. Furthermore, results of in situ hybridization show that miR‐663 expression is correlated with Gleason score and TNM stage and is an independent prognostic predictor of clinical recurrence. Together, these findings suggest that miR‐663 is a potential oncomiR for CRPC and may serve as a tumor biomarker for the early diagnosis of CRPC. J. Cell. Physiol. 229: 834–844, 2014. © 2013 Wiley Periodicals, Inc.