Taiwan is an endemic area of hepatitis B virus (HBV). All previous studies have concluded that HBV is the major cause of hepatocellular carcinoma (HCC) in Taiwan. An HBV- and hepatitis C virus (HCV)-endemic township, Tzukuan, in southern Taiwan has been identified with the prevalence of 24% for HB surface antigen (HBsAg) and 37% for anti-HCV antibodies. To elucidate the aetiology of HCC and impact of HCV in this township, we conducted a case-control study and compared HBV-related liver cancer mortality in Tzukuan and Taiwan as a whole. Based on cancer registration datasets of 2 medical centres from 1991 to 1995, we recruited 18 male and 9 female HCC cases from the study township. Their mean age (+/-standard deviation) was 60.3 (+/- 7.3) years. Randomly sampled from a community-based survey, 4 age- (+/- 2 years) and sex-matched residents were selected as community controls for each HCC case. The HBsAg carrier rate was 40.7% in cases and 25.0% in controls (P = 0.1). Anti-HCV positive rate was 88.9% in cases and 53.7% in controls (P = 0.008). Age-adjusted liver cancer mortality in Tzukuan (36.5 per 10 5 ) was significantly higher than that of Taiwan as a whole (20 per 10 5 ). Based on the HBsAg-positive rate among HCC patients (40.7% in Tzukuan and 77.4-86.6% in Taiwan), the estimated HBV-related liver cancer mortality was similar in Tzukuan (14.9 per 10 5 ) and Taiwan (15.8-17.3 per 10 5 ). We concluded that HCV was the major risk factor for excess liver cancer mortality in this HCV-endemic township of the HBV-endemic country.