Background: MicroRNA-493 (miR-493) was upregulated in prostate cancer (PCa). This study was designed to investigate the mechanism underlying miR-493 mediated pro-proliferation in PCa cells. Methods: Expression of miR-493 in PCa cell lines (DU145 and PC3) and control cells was determined using qRT-PCR. PCa cells were transfected with miR-493 mimics, inhibitor, negative control (NC), PH domain leucine-rich-repeats protein phosphatase 2 (PHLPP2), and Akt expressing plasmids and Akt inhibitor MK-2206. Cell proliferation, quantitative expression of miRNA and mRNA were detected. Protein expression was determined using western blotting analysis. Results: Results showed that miR-493 in PCa cells was upregulated compared with RWPE-1 cells. Cells transfected with miR-493 mimics or inhibitor significantly reduced or enhanced expression of PHLPP2 (p < 0.05), respectively. Cell proliferation was significantly enhanced by miR-493 overexpression, or inhibited by PHLPP2 overexpression. The administration of Akt inhibitor MK 2206 attenuated miR-493-enhanced cell proliferation. PCa cells transfected with Akt express vectors partially enhanced PHLPP2-reduced cell proliferation. Conclusions: These results demonstrated that miR-493 acted as a onco-miR in PCa cells and promoted PCa cell proliferation via inhibiting tumor suppresser PHLPP2 expression and activating Akt signaling pathway.