To determine the role of hepatitis C virus (HCV) infection in the aetiology of hepatocellular carcinoma (HCC) in Zimbabwe, HCV antibodies (anti-HCV) were determined in sera from 63 HCC patients using a second generation enzyme immunoassay. Anti-HCV was found in 15 patients (23.8%), 12 of whom (80%) were males. The mean ages of anti-HCV positive and anti-HCV negative patients were 62.1 (SD = 10.6) and 44.3 (SD = 15.2) years, respectively (P < 0.001). HIV antibodies were found in 17/59 patients (28.8%), 12 of whom (70.6%) were males. The mean ages of HIV positive and HIV negative patients were 39.4 (SD = 15.2) and 51.0 (SD = 15.2) years (P = 0.011). Hepatitis B surface antigen (HBsAg) was detected in 26/61 patients (42.6%) with mean ages of HBsAg positive vs negative patients of 41.5 (SD = 15.4) years for HIV positive and 53.1 (SD = 15.1) years for HIV negative subjects (P = 0.005). Younger HCC patients had high prevalences of HBsAg and anti-HIV and a low prevalence of anti-HCV; while older patients had a high prevalence of anti-HCV and low prevalences of HBsAg and anti-HIV. This study suggested that HCV infection is probably an important aetiological agent of HCC in Zimbabwe; however, the role of HIV infection as a cause of HCC either singly or as a co-factor with hepatitis B virus infection remains speculative and warrants further study.