Abstract MicroRNAs (miRNAs) are small, noncoding RNAs which can often act as an oncogene or a tumor suppressor. Several miRNAs are associated with the development of hepatocellular carcinoma (HCC). We demonstrated that miR-125b significantly suppresses HCC cell proliferation and promotes apoptosis by inhibiting the gene expression of the anti-apoptotic protein, Bcl-2. Bioinformatic analysis indicated that the 3′UTR of Bcl-2 has binding sites for miR-125b. Luciferase reporter assay confirmed the ability of miR-125b to dramatically suppress Bcl-2 transcription, suggesting that Bcl-2 is a target gene for miR-125b. We concluded that miR-125b acts as a tumor suppressor in hepatic tumor development by targeting Bcl-2 and inducing cancer cell apoptosis.