To study the relationship between hepatocellular carcinoma (HCC) and hepatitis C virus (HCV), sera from 178 patients with HCC and 194 blood donors from Maputo, Mozambique were tested for antibodies to HCV (anti-HCV) using a second generation enzyme-linked immunosorbent assay and a confirmatory test with six synthetic peptides as reagents. The presence of hepatitis B surface antigen (HBsAg) was tested using an enzyme immunoassay. The prevalence of anti-HCV was higher in patients with HCC than in controls, but the difference was not significant after adjustment for age. Therefore, this difference reflected a difference in the age structure between the two groups. The prevalence of HBsAg was higher in patients with HCC than in controls. There was a negative association between anti-HCV and HBsAg in patients with HCC that was not significant after adjustment for age. These serologic results, which contrast with previous reports, show the need for further studies on the relationship between HCC and HCV using second generation serologic tests and molecular biology techniques.