Hepatocellular carcinoma (HCC) has variable 18F-fluoro-2-deoxy-D-glucose (18F-FDG) uptake and the relationship between 18F-FDG uptake with the expression of glucose transporters (Gluts) and hexokinase II (HK-II) has not been extensively examined. Present study explored the role of 18F-FDG positron emission tomography (PET) as a clinical significance and the association with Gluts and HK-II in patients with HCC. Whole body 18F-FDG PET, immunohistochemistry and western blot analysis of Glut-1 to Glut-5 and HK-II were performed in 31 patients (24 male and 7 female, range 48-75 years) with HCC. Significant correlation was found between 18F-FDG uptake and overall expression of Glut-2 (rho=0.55, p=0.002) and HK-II (rho=0.37, p=0.04). Expression of HK-II was correlated with Glut-2 (rho=0.57, p=0.0009) but not with other Gluts, which indicated that Glut-2 is a major glucose transporter. The prognosis of patients with SUV >/=2 and positive Glut-2 were significantly worse than that with SUV <2 and negative Glut-2 (p=0.005 and p=0.03), respectively. Multivariate analysis showed that SUV and lymph node metastasis were independent prognostic factors. The present study indicated that combined evaluation of 18F-FDG uptake and expression of Glut-2 might have an important role for management of patients with HCC.