Aberrant expression of the Cullin 4A (CUL4A) is found in many tumor types, but the functions and mechanism of CUL4A in prostate cancer (PCa) development and progression remain largely unknown. The aim of this study was to investigate the possible role of CUL4A in prostate tumorigenesis. Immunohistochemistry was used to examine CUL4A expression in human PCa tissues and BPH tissues. Cell proliferation was assessed by MTT, and migration and invasion were analyzed by Transwell and Matrigel assays after CUL4A knockdown in PCa in vitro. The results showed that CUL4A protein was overexpressed in 86.21 % of PCa tissues. CUL4A knockdown with siRNA in PCa cells decreased cell proliferation, migration, and invasion. Mechanistically, CUL4A could modulate the expression of P53 in PCa cells. Our results indicate that CUL4A overexpression play an oncogenic role in the pathogenesis of PCa, and CUL4A may be a potential therapeutic target for PCa.