Hepatitis-B viral (HBV) infection and schistosomiasis are among the most common causes of liver cancer (hepatocellular carcinoma; HCC) in Egypt. The present study investigates the effects of both infectious diseases and other demographical and environmental factors on the risk of HCC among a representative group of Egyptian patients with HCC (n = 102) and controls with no signs of hepatopathology (n = 96). Factors associated with an increased risk of HCC in Egypt were age over 60 yrs-old, farming, cigarette smoking and occupational exposure to chemicals such as pesticides. However, schistosomiasis (relative risk, RR: 5.22; 95% confidence intervals, C.I.: 2.93-9.31) and HBV infection (RR: 12.51; 95% C.I.: 6.11-25.59) were the major risk factors in the development of HCC. Schistosomiasis increased the severity of HBV infection and elevated the risk of HCC over that associated with the HBV infection alone. Understanding these relationships may enable us to determine the susceptibility to HCC among high risk groups and to provide these individuals with effective measures for early prevention or intervention.