The AKT pathway serves important roles in tumor cell growth. Its overexpression is associated with poor prognosis in a number of types of cancer; however, the role of AKT in the role of the pathogenesis of hepatocellular carcinoma (HCC) remains unclear. The present study was undertaken to explore the clinical relevance of phosphorylated AKT (p-AKT) in HCC. The level of p-AKT in tumor (TU) and paired adjacent normal liver (AN) tissue from 202 HCC patients was evaluated with immunohistochemistry. The results demonstrated that p-AKT was more highly expressed in TU than in AN tissue. Kaplan-Meier curves and Cox regression revealed that patients with a high expression of p-AKT (AN) exhibited reduced overall and relapse-free survival times; this was not observed at a statistically significant level in p-AKT (TU). Additionally, the high expression of p-AKT (AN) was positively correlated with hepatitis C virus (HCV) infection in HCC patients. These results support the hypothesis that AKT activation is a mechanism of HCV-induced hepatocarcinogenesis, suggesting that AKT can be a therapeutic target for the treatment of recurrent HCC subsequent to surgical resection.