Angiogenesis and coagulation system activation are associated with tumor growth and metastasis. Vascular endothelial growth factor (VEGF) has been reported to play a major role in tumor angiogenesis. The elevation of plasma D-dimer level indicates the activation of coagulation and fibrinolysis. The purpose of this study was to: (a) evaluate the correlation between serum VEGF and plasma D-dimer level; (b) analyze the clinical features that might affect the VEGF and D-dimer levels in patients with hepatocellular carcinoma.Twenty patients with hepatocellular carcinoma were included prior to treatment. Serum VEGF levels were measured by enzyme-linked immunosorbent assay. Plasma D-dimer levels were measured by quantitative latex microparticle enhanced turbidimetric immunoassay.The presence of a high plasma D-dimer level was found to be correlated with the presence of central necrosis, higher Child's grade, advanced TNM stage, and the presence of portal vein thrombosis when plasma D-dimer levels were compared between different clinicopathologic groups. Tumors larger than 2 cm in diameter had higher median serum VEGF levels than tumors less than 2cm in diameter. No correlation was found between plasma D-dimer level and serum VEGF level in hepatocellular carcinoma patients (r=0.126, p=0.598).No correlation was found between the plasma D-dimer level and the serum VEGF level in hepatocellular carcinoma patients. The plasma D-dimer level appeared to reflect the tumor stage and vascular invasion of hepatocellular carcinoma. Serum VEGF level in hepatocellular carcinoma patients showed a positive correlation with tumor size.