The prognosis of the hepatocellular carcinoma is influenced by its invasion and metastasis. Interacting with a number of oncogenes, HBV infection is a high risk factor for HCC. Overexpression of Focal adhesion kinase (FAK), a novel oncogene, has been suggested to play an important role in tumorigenesis and progression of many cancers, including HCC. However, the relationship between HBV infection and FAK for HCC prognosis is still unclear. A retrospective study of 89 archival specimens of subjects with histologically confirmed HCC was carried out. Immunohistochemistry was utilized to examine the expression of FAK. Then the FAK expression was analyzed with index of HCC, especially with HBsAg and HBV DNA. FAK overexpression was detected in 38/89 of the tumors. FAK overexpression in HCC significantly correlated with HBsAg (P = 0.033), HBV DNA level (P = 0.005), vascular invasion of HCC (P = 0.000*), and TNM stage (P = 0.003). FAK-positive patients exhibited a lower survival rate compared with those with negative FAK expression. Overexpression of FAK might have a correlation with HBV infection and contribute to HCC progression, raising the possibility of FAK overexpression as a potential marker for a poor prognosis in HCC.