Aberrant activation of the Wnt/β-catenin signal pathway is frequently observed in hepatocellular carcinoma (HCC). β-Catenin is the major cellular effector of Wnt signaling and inactivation of adenomatous polyposis coli (APC) results in nuclear accumulation of β-catenin. Therefore, it was speculated that APC inhibition could play important roles in activating the Wnt/β-catenin pathway and in HCC progression. In this study, we report that miR-106b expression is markedly upregulated in hepatoma cells and hepatoma tissues compared with immortalized normal liver epithelial cells and normal hepatic tissues. Ectopic expression of miR-106b induces the proliferation and anchorage-independent growth of hepatoma cells, whereas inhibition of miR-106b reduced this effect. Furthermore, miR-106b upregulation in hepatoma cells modulated entry into the G(1)/S transitional phase by upregulating cyclin D1 and downregulating APC. Moreover, we demonstrated that miR-106b downregulates APC expression by directly targeting the 3'-untranslated region of APC messenger RNA. Taken together, our results suggest that miR-106b plays an important role in promoting the proliferation of human hepatoma cells and presents a novel mechanism of micro RNA-mediated direct suppression of APC expression in cancer cells.