To assess whether hepatitis C virus infection was a risk factor for the development of non-alcoholic liver cirrhosis, antibody to hepatitis C virus (anti-HCV; detected by a second generation HCV enzyme immunoassay), hepatitis B surface antigen (HBsAg; detected by radioimmunoassay) were tested in 150 cirrhotics and 150 sex-matched and age-matched healthy controls. The prevalence of anti-HCV and HBsAg in cirrhotics was higher than in controls (22.0%, 73.3% vs. 2%, 18.7%; P = 0.001). The prevalence of anti-HCV in HBsAg-negative cirrhotics (45.0%) was higher than that in HBsAg-positive patients (13.6%; P = 0.001). Both the anti-HCV and carriage of HBsAg were associated significantly with liver cirrhosis, showing odds ratio of 12.0 for HBsAg carriers and 13.8 for patients with anti-HCV. Compared with those without HBsAg and anti-HCV, there was a significantly positive linear trend for developing cirrhosis with the presence of HBsAg alone (odds ratio = 19.9), anti-HCV alone (odds ratio = 49.0), and those positive for HBsAg and anti-HCV (odds ratio = 81.8) (P = 0.00001). The population-attributable risk for developing liver cirrhosis was estimated as 10.8% for anti-HCV alone, 55.2% for HBsAg alone, and 9.4% for both anti-HCV and HBsAg in southern Taiwan. In conclusion, this study shows that hepatitis B and C virus infection act independently and synergistically in the development of non-alcoholic liver cirrhosis among Chinese in Taiwan.