To investigate the influence of hepatitis C virus (HCV) infection on patients with chronic hepatitis B virus (HBV), the presence of antibody against C100-3 antigen of HCV (anti-HCV) was examined in 420 patients with chronic HBV infection and 275 healthy subjects. It was found that the prevalence of HCV infection increased in parallel with the severity of liver damage. The positive rates of anti-HCV were as follows: healthy subjects, 2.9% (8/275); asymptomatic carriers, 2.6% (5/193); chronic hepatitis, 5.2% (3/58); liver cirrhosis, 11.4% (8/70); hepatocellular carcinoma (HCC), 12.1% (12/99). To elucidate the interaction of these two viruses in hepatocellular carcinoma, 128 HCC patients and 384 age-matched and sex-matched subjects were further analyzed. Eighty-seven of 128 HCC patients (68.0%) were only positive for HBsAg, 13 patients (10.1%) were only anti-HCV positive, and 12 (9.4%) were positive for both markers. The presence of HBsAg and anti-HCV was associated strongly with HCC. Moreover, the risk of HCC was significantly higher when both HBsAg and anti-HCV were present simultaneously. These results suggested that concurrent HCV infection might accelerate the progression of chronic HBV infection and may contribute to the pathogenesis of HCC in patients with chronic HBV infection.