Abstract: Objective To investigate the expression of MKP-4 in hepatocellular carcinoma（HCC）and its clinical significance. Methods From January 2005 to December 2010，100 cases of HCC resection and corresponding paracancerous tissues were collected in Affiliated Hospital of Nantong University. Immunohistochemistry（SP method） was used to detect MKP-4 expression in above tissues. Correlations between MKP-4 expression and clinicopathological parameters and prognosis were analyzed. Another 8 cases of fresh HCC and paracancerous tissues were collected，and the expression of MKP-4 was detected by Western blotting methods. Results The expression level of MKP-4 protein in 8 cases of fresh HCC tissues was 0.611± 0.136，which was significantly lower than 0.931±0.107 of paracancerous tissues（P＜0.05）. The high expression rate of MKP-4 in HCC tissues was 20％，lower than 34％ of paracancerous tissues，and the difference was statistically significant（P＜0.05）. The expression of MKP-4 was correlated with histological grade（P=0.047），vein invasion（P=0.026）and TNM stage（P=0.036）. Kaplan-Meier analysis indicated that the median overall survival of MKP-4 low expression group was 52 months, and that of high expression group was unachieved, which was longer than MKP-4 low expression group（P＜0.05）. Conclusion MKP-4 exerts as a tumor suppressor gene in the development and progression of HCC，which suggests that MKP-4 may play as a potential therapeutic target and an efficient prognosis biomarker for HCC.