Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and effective therapy for human liver cancer remains a difficult clinical concern. Researchers have demonstrated that microRNAs play important roles in the tumorigenesis and tumor progression of human liver cancer; therefore, regulation of microRNAs may be a new strategy for HCC therapy. MicroRNA-196a (miR-196a) has been reported to be overexpressed in many types of cancers. However, the regulatory effects of miR-196a in human liver cancer are not fully understood. In the present study, we found that miR-196a was overexpressed in human liver cancer cells compared to that observed in normal liver cells. MTT and colony formation assays indicated that downregulation of miR-196a inhibited liver cancer cell proliferation which was due to the induction of cell apoptosis. A mouse model demonstrated that downregulation of miR-196a also inhibited human liver cancer cell migration and invasion in vivo. Further study indicated that FOXO1 is a direct target of miR-196a, and inhibition of FOXO1 promoted human liver cancer cell growth. Taken together, the present study demonstrated that the expression of miR-196a in human liver cancer cells was upregulated; downregulation of miR-196a regulated human liver cancer cell biological functions which could benefit the clinical therapy of human liver cancer in the future.