Estimated 500,000 - 1 million cases of hepatocellular carcinoma (HCC) are reported to occur yearly worldwide, with a mean annual incidence of around 3 – 4% of global population. HCC is rapidly fatal in most patients; that makes its incidence and mortality rates almost equal. In the last 5–10 years there were many alarming reports of sharply increased incidence of HCC. In Egypt, HCC reported to account for about 4.7% of chronic liver disease (CLD) patients, which has tremendous impact on socio-economic development in the country. Available data suggests indirect evidence of an association between Schistosoma mansoni and hepatocellular carcinoma, possibly through potentiation of hepatitis infections. The present study was conducted case control analysis of 60 HCC patients. Chronic schistosomiasis cases were confirmed by finding Anti-Schistosoma mansoni antibodies IgG by ELISA. Hepatitis C viral infection was proved by detection of viral load by quantitative Real time PCR. Among the study group 56.6% (34/60) were dweller in rural in Al-Fayoum governorate. Within hepatocellular carcinoma cases 26.7% (16/60) and 33.3% (20/60) suffered mono chronic schistosomiasis and mono hepatitis C (HCV) infections respectively, with no statistically significant differences (p=0.37), indicating comparable risk value of both infections in predisposing directly to HCC. Additionally; frequency of HCC patients with assumed potentiated HCV infection by chronic Schistosoma mansoni 6.7% (4/60) were statistically significant (p<0.05) less among total HCC patients included in this study, when compared to HCC patients preceded by either pure chronic schistosomiasis 26.7% (16/60) or pure HCV infection 33.3% (20/60). Our present study is one of few, addressing the possibility of direct relation between S. mansoni & hepatic carcinoma, concluding an initial indication of equal risk value of both human chronic S. mansoni infection and hepatitis C viral infections in precipitating hepatocellular carcinoma among Egyptian patients.