Background: Hepatocellular carcinoma (HCC) is one of the very frequent malignancies that has poor prognosis. Chronic hepatitis B is the most important risk factor in the world particularly in developping countries. In developed world, HCC occurs in the background of chronic infection with HCV or alcohol abuse. Several factors affects the development of HCC in chronic hepatitis patients including viral genotype. Objectives: The aim of this study was to determine HCV and HBV viral profile in Egyptian and Yemeni HCC patients. Additionally, HCV and HBV were genotyped to investigate any possible correlation with HCC development. Methodology: Thirty HCC Egyptian patients admitted to the Hepatology Unit, Medical Research Institute, Alexandria University and thirty HCC Yemeni patients attending the oncology center in Al-Gomhory hospital in Sanaa have been enrolled in this study. Hepatitis B surface Ag (HBs-Ag) was not detected in Egyptian HCC patients but in 36.7% of Yemeni HCC patients. On the other hand, anti-HCV antibodies were detected in 93.3% of the Egyptian HCC patients and in 16.7% only in Yemeni patients. HBV genotyping by direct sequencing of pol gene showed 11 cases of genotype D and 1 case of genotype E among HCC Yemeni patients. HCV genotyping by sequencing of NS5b and 5'UTR showed 21 cases of genotype 4 and 2 cases of genotype 1 and genotype 2 among Egyptian HCC patients. Conclusion: From the current study HCC appears to be significantly associated with HBV and HCV chronic infections in Yemen and Egypt respectively. In Egypt, occult HBV co-infection might escalate the danger of HCC development among HCV patients.