The clinical significance of phosphatase and tensin homolog deleted on chromosome ten (PTEN) protein expression and the correlation between the expression of PTEN and phosphorylation of protein kinase B (PKB/AKT) in human hepatocellular carcinoma (HCC) were investigated.The expression of PTEN and phospho-AKT was detected by SP immunohistochemical technique and Western blotting in 35 cases of HCC, 15 cases of liver cirrhosis and 8 cases of normal tissues. The correlation between the expression of PTEN and PKB/AKT in HCC was analyzed. The results showed that the positive expression of PTEN in HCC (62.9 %, 0. 085±0. 021) was significantly lower than that in liver cirrhosis and normal tissues (P＜0.01). The expression level of PTEN was related to the differentiation degree of HCC and the status of metastasis (P＜0. 05). Western blotting revealed a significant inverse correlation between PTEN and phospho-AKT (r=-0. 818, P＜0.01). These results demonstrated that down-regulation or loss of PTEN, which may not be able to effectively inhibit the hyper-phosphorylation of PKB/AKT, might play an important role in tumorigenesis and progression of HCC.