MicroRNAs (miRNAs) are small, noncoding RNAs which can bind to target mRNAs and regulate gene expression. Increasing evidences suggest that miRNAs play an important role in driving hepatocellular carcinoma (HCC) progression by regulating tumor cell proliferation, apoptosis, invasion, and migration. In this study, we demonstrated that the expression of microRNA-30a-3p (miR-30a-3p) was reduced in HCC cell lines in comparison to immortalized liver cell line, LO2. Augmented miR-30a-3p level markedly inhibited MHCC-97H cell growth, migration and invasion in vitro. MiR-30a-3p was also found to inhibit tumor growth in vivo using tumor-bearing mice. Mechanismly, COX-2 was discovered to be a direct and functional target of miR-30a-3p in MHCC-97H cells. Raised miR-30a-3p expression reduced the transcriptional level of COX-2 in MHCC-97H cells, while genetically upregulated COX-2 expression was able to reverse the function of miR-30a-3p-mediated suppression of MHCC-97H cells growth, migration and invasion. In addition, we found that using a COX-2 inhibitor, celecoxib, could enhance the anti-metastatic role of miR-30a-3p in MHCC-97H cells. Lastly, we found that decreased COX-2 protein level affected PGE2 production, leading to lower Bcl-2, Caspase-3, MMP2 and MMP9 expression but higher Bax and E-cadherin expression, which in turn culminated in higher rates of cell death and lower rates of cell migration. Taken together, our findings demonstrate that miR-30a-3p could be a target for the treatment of hepatocellular carcinoma cells progression.© The author(s).