There is no reliable marker available for early detection, diagnostic confirmation, or disease prognosis available of prostate cancer (PCa). We aimed to evaluate the function of Cullin-1 and unravel its underlying molecular mechanism to develop novel treatment options equivalent to PCa.We used immunohistochemistry to analyze the correlation between Cullin-1 expression and clinicopathologic variables and patient survival. The Cullin-1 level was tested in PCa cells. The role of regulation of Cullin-1 in PCa was applied in vitro and vivo. In addition, we further investigated the signaling pathway of Cullin-1 in prostate cancer cell proliferation.We first discovered that Cullin-1 expression was upregulated in human PCa tissues and inversely related with PCa differentiation. We then found that high expression of Cullin-1 protein suggested a poor prognosis in PCa patients. Also, Cullin-1 promotes PCa cell proliferation in vitro and tumor growth in vivo. We then found that the mechanism of Cullin-1 regulation on cell-cycle progression is due to increased expression of p21 and p27, and decreased expression of cyclin D1 and cyclin E after Cullin-1 knockdown.Cullin-1 exerts multiple biological effects in the PCa cell line. Through promoting proliferation and by countering cisplatin-induced apoptosis, Cullin-1 has been deeply implicated in the pathogenesis and development of PCa.