Objectives: The aim was to evaluate expression of EGFR and TGF-α in HCV, cirrhosis and HCC; to assess the relationship between EGFR, and/or TGF-α and risk of development of HCC. This could guide to the identification of the benefit of using antagonists to these markers to prevent transformation of HCV infection HCC. Material And Methods: This study was done on 40 liver core biopsies from patients with viral C infection, 20 liver core and wedge biopsies from hepatocellular carcinoma cases and 5 control cases. All were stained with EGFR and TGF-α. Some selected HCC cases were submitted for Fluorescence In situ hybridization. Results: IHC expression of EGFR and TGF-α was stronger in HCC and cirrhosis cases compared to HCV cases; as well as stronger in higher grades of activity and higher stages of fibrosis of HCV cases compared to lower ones. However FISH positive results was detected only in 33.3% of HCC cases. Conclusion: EGFR and TGF-α could be used as indicators for carcinogenesis in HCV lesions, and as prognostic indicators in follow up of HCC. So usage of antagonists to them in HCV patients could be useful in protecting from progression to HCC.