Angiogenesis occurs in response to tissue damage, and is of vital importance for tumor growth and metastasis. Basic fibroblast growth factor (bFGF), a well-known angiogenic factor, has been suggested to be a useful diagnostic marker in certain hypervascular tumors. However, the relevance of its detection has not been well evaluated in patients with hepatocellular carcinoma (HCC) and benign chronic liver diseases. In the current study, immunoassay of bFGF was performed on serum samples from 39 patients with HCC, 21 with liver cirrhosis, 22 with chronic hepatitis and 40 normal subjects. The serum bFGF level was significantly increased in patients with liver cirrhosis and HCC when compared with those with chronic hepatitis or normal subjects (all p-values < 0.001). However, no difference was observed between the groups with liver cirrhosis and HCC (p > 0.05). If we set 9.6 pg/ml (mean + 3 standard deviations of bFGF in the control group) as the upper limit of normal serum level of bFGF, elevated bFGF concentrations were noted in 9.1%, 42.9% and 51.3% of patients with chronic hepatitis, liver cirrhosis and HCC respectively. In non-cancer patients, the coexistence of acute illness (p = 0.000) was an independent factor related to the elevation of serum bFGF. On the other hand, a multivariate analysis demonstrated that both advanced stage of cancer (p = 0.026) and coexistence of acute illness (p = 0.000) influence the serum level of bFGF in patients with HCC. We conclude that serum bFGF levels are significantly higher in patients with HCC and are positively correlated with advanced tumor stage. Nevertheless, elevation of serum bFGF may also be observed in a significant number of patients with liver cirrhosis. Therefore, measurement of serum bFGF alone cannot be satisfactory as a tumor marker for diagnosis of HCC. In addition, it is important to point out that coexistence of acute illness may be a crucial confounding factor in the diagnosis or monitoring of any cancer by the estimation of serum bFGF.