Hepatitis C infection is an emerging epidemic. Hepatitis C virus is a major cause of morbidity and mortality in Egypt. The mechanisms leading to liver cell injury, inflammation and fibrosis in chronic hepatitis C, are not fully understood. Apoptosis have been postulated as a mechanism of liver cell injury in chronic hepatitis C. Apoptosis is a form of cellular death in which the cell breaks up into several apoptotic bodies that are phagocytosed by the phagocytic system without any evidence of inflammatory reaction. Fas antigen is an important mediator of apoptosis. Overexpression of P53 has been extensively studied in HCC, but fewer observations have been made in non-tumoral liver diseases. The aim of this study was to detect the role of apoptosis as a mechanism of liver cell injury in chronic hepatitis C and to correlate it with the degree of liver cell injury. In this study, the immunohistochemical technique was used to localize the extent of expression of both Fas antigen and P53 in liver tissues with chronic hepatitis C of various grades of inflammatory activity. One hundred and twenty seven patients with clinical and/or laboratory evidence of chronic liver disease referred to Tropical Medicine Department, Theodor Bilharz Research Institute over a period of two years, were surveyed for the presence of HCV infection were subjected to full clinical, laboratory, abdominal ultrasonographic and endoscopic examinations. 57 patients selected for this study having chronic hepatitis C virus infection were subjected to PCR for detection of viraemia levels and liver biopsy for histopathological assessment of the degree of liver cell injury and of the stage of liver fibrosis. Five healthy individuals were included in this study to serve as controls. Liver tissues of both patient and control groups had been examined by immunohistochemical techniques (detection of both Fas expression for apoptosis and p53 expression for liver cell proliferation) for detection of apoptosis. Electron microscopic study of liver tissues of 8 patients done to study the detailed ultrastructural features of liver cell apoptosis. The current study showed Fas positivity in 84.2% of the patient group pointing to the prevalence of the apoptotic process in chronic hepatitis C. Significant direct correlations were detected between grading of inflammation, staging of fibrosis, serum ALT, AST, ALP and HCV-RNA levels relative to Fas positivity in HCV-infected patients. In the present study, p53 nuclear accumulation was detected in only 29.8% of the studied HCV cases. Significant direct correlations were detected between grading of inflammation, staging of fibrosis, serum bilirubin and albumin, ALP and HCV-RNA viraemia levels relative to p53 positivity in chronic HCV patients. However, no significant correlation was detected between either serum ALT level or serum AST level relative to p53 positivity in our study group. High significant direct correlation was detected between p53 positivity and Fas positivity. Significant direct correlations were detected between hepatic steatosis and both Fas positivity (p<0.05) and p53 positivity (p<0.01). The extent of apoptosis (Fas antigen expression) could point to the degree of activity in chronic viral C hepatitis. P53 is over expressed in the precocious stages of HCV-related liver damage before carcinogenesis.