Background: Overexpression of epidermal growth factor (EGF) in the liver induces transformation to hepatocellular carcinoma(HCC) in animal models. Polymorphisms in the EGF gene modulate EGF levels. Objective: to evalute the effect of EGF gene single nucleotide polymorphism and assess its correlation with risk of hepatocellular carcinoma in patient with chronic liver diseases. Patients and Methods: The present study included 77 subject, divided into 4 groups; Group 1: included 17 asymptomatic healthy control volunteers who matched with age and sex, Group 2: included 20 patients with chronic hepatitis C infection, Group 3: included 20 patients with liver cirrhosis and Group 4: included 20 patients with hepatocellular carcinoma. For all subjects the following investigations were performed; complete blood count, Liver functions tests. Sero markers of hepatitis viruses HBsAg, total anti-HBC, and HCV-RNA by quantitative PCR and Alfa fetoprotein, in addition to full history taking including risk factors of HCV infection, thorough clinical examination and abdominal ultrasongraphic examinations were done. One ml blood was taken on EDTA for DNA extraction and detection of single nucleotide polymorphism of the EGF by polymerase chain reaction (PCR) and restriction enzymes followed by agarose gel electrophoresis stained with ethidium bromide. Results: The control subjects with GG and GA genotypes had 7.875 and 3.375 folds odds ratio for developing HCC and the control group with GG and GA genotypes had 2.571 and 1.929 folds for developing cirrhosis than AA genotype respectively. The cirrhotic patients with GG and GA genotypes had 3 and 1.75 folds for developing HCC respectively and the chronic hepatitis C patients with GG genotype had 2.333 folds of developing HCC than AA genotype. Conclusion: The EGF 61 A/G polymorphism might be associated with a high risk for the development of HCC in both chronic liver disease patients and normal healthy subjects and a risk factor for cirrhosis development in normal healthy subjects.