FOXK1 (forkhead box k1), a member of the FOX family, is overexpressed in several types of solid tumors. However, the biological function of FOXK1 in hepatocellular carcinoma (HCC) remains poorly understood. In the present study, we investigated the expression status and functional roles of FOXK1 in HCC. Our results demonstrated that the expression of FOXK1 was significantly up-regulated in human HCC tissues and cell lines. In addition, down-regulation of FOXK1 suppressed the proliferation, migration and invasion of HCC cells in vitro, as well as attenuated tumor growth in nude mice model. We further elucidated that knockdown of FOXK1 down-regulated the protein expression levels of β-catenin, c-myc and cyclin D1 in HepG2 cells. In conclusion, the present study indicated that FOXK1 may act as an oncogene in human HCC, and knockdown of FOXK1 significantly inhibited HCC cell proliferation, migration and invasion, partly through the inactivation of Wnt/β-catenin signaling pathway. These findings suggest that FOXK1 may be a novel therapeutic target to treat HCC.