Objective To investigate the expression of arginase-2 (Arg-2) in hepatocellular carcinoma (HCC) tissues and to discuss its clinicopathological significance. Methods Totally 113 HCC samples and corresponding adjacent liver tissues were collected. Among them 29 cases were characterized by the presence of dysplastic nodules (DN). Another 12 samples of normal liver tissues were collected as controls. Western blotting analysis was used to detect the Arg-2 protein expression in 15 HCC samples, corresponding adjacent liver tissues and 12 control samples. Immunohistochemical staining was performed to detect the Arg-2 expression in 113 HCC samples, corresponding adjacent liver tissues and DN samples. The correlation of Arg-2 expression with clinicopathological features of HCC was analyzed. Results Western blotting analysis revealed no Arg-2 expression in adjacent liver tissues and normal liver tissues, while the expression was significantly increased in HCC tissues (P<0.01). Immunohistochemical staining showed that Arg-2 was expressed in the cytoplasm of HCC cells, with a positive rate of 77.0% (87/113). Arg-2 expression was found to be correlated with the histological grades of HCC tissue (P<0.05). Arg-2 was not expressed in low-grade DN; its positive rate was 14.3% (2/14) in the high-grade DN and 66.7% (8/12) in well-differentiated HCC (P<0.05). Conclusion Arg-2 is highly expressed in the HCC tissues and its expression is associated with histological grades of HCC, and it may be involved in the development and progression of HCC. Detecting Arg-2 expression may help to differentiate HCC from DN.