AbstractBackground and Aim:  DOC‐2/DAB2 interactive protein gene (DAB2IP) is a novel member of the Ras GTPase‐activating protein family and plays a tumor suppressive role in cancer progression, but its function in hepatocellular carcinoma (HCC) remains unclear. This aims of this study were to analyze the clinicopathological features of DAB2IP expression in HCC, and to determine the effect of DAB2IP on HCC cell behaviors in vitro.Methods:  The expression of DAB2IP was detected in hepatocyte cell line and HCC cell lines by real‐time reverse transcription‐polymerase chain reaction and western blot. DAB2IP expression was then examined in 120 cases of clinical paraffin‐embedded HCC tissue by immunohistochemistry (IHC). 3‐(4,5)‐dimethylthiahiazo (‐z‐y1)‐3,5‐di‐ phenytetrazoliumromide (MTT) method and in vitro invasive assay were finally performed to evaluate the effect of DAB2IP depletion on cell proliferation or invasion of HCC cells.Results:  DAB2IP expression was lower in HCC cell lines or tissues than in hepatocyte cell lines, adjacent cirrhotic livers or normal livers (P < 0.05). Its expression was positively correlated with tumor size (P = 0.01). Patients with lower DAB2IP expression had shorter overall survival time (P = 0.013). DAB2IP suppresses proliferation and invasion of HCC cells in vitro.Conclusion:  DAB2IP is a valuable marker for progression of HCC patients. Downregulation of DAB2IP is associated with poor prognosis in HCC patients. DAB2IP silence alone is sufficient to promote HCC cell proliferation and invasion in vitro.