Objective: To investigate the DLC2 protein expression and its correlation with expression of RhoA and prognosis in hepatocellular carcinoma (HCC) patients. Methods: Western blotting and immunohistochemical staining were employed to detect DLC2 protein expression in 128 HCC specimens. The correlation between DLC2 protein expression and clinicopathological characteristics and prognostic value of DLC2 for HCC patients were analyzed. Results: HCC tissues revealed significantly lower level of DLC2 protein than pericarcinomatous liver tissues (PCLT) (P<0.05). There was a significant correlation between underexpression of DLC2 protein and cell differentiation (P<0.05). Meanwhile, underexpression of DLC2 protein was correlated with overexression of RhoA. Furthermore, HCC patients with DLC2-negative expression showed a significantly poorer prognosis than those with DLC2-positve expression. Conclusion: Our data indicates that decreased DLC2 expression in HCC correlates with cell differentiation of HCC and overexpression of RhoA, and underexpression of DLC2 is associated with poor prognosis in HCC patients.