The prognosis and survival rate of prostate cancer are very poor. Previous studies have shown that miR-556-5p have emerged as important regulators in cancer cell biological processes. The role of miR-556-5p in prostate cancer remains unclear. In this study, expression of miR-556-5p in prostate cancer cell lines and tissues was upregulated. Result of MTT assays, colony formation and anchorage-independent growth assays demonstrated that overexpression of miR-556-5p promoted prostate cancer cell growth. Additionally, PPP2R2A was identified as a direct target of miR-556-5p. Ectopic expression of miR-556-5p led to downregulation of PPP2R2A protein, which resulted in the downregulation of p27, upregulation of cyclin D1. Taken together, our data provide compelling evidence that miR-556-5p functions as an onco-miRNA and participates in prostate cancer carcinogenesis by suppressing PPP2R2A expression.