Abstract Background: TBI (Traumatic Brain Injury) is a worldwide leading cause of death and disability. Liver cirrhosis is known as a significant risk factor for increased morbidity and mortality in trauma patients. HCV (Hepatitis C Virus) is a major cause of liver cirrhosis worldwide especially in Egypt which has the highest HCV prevalence all over the world. Aim of Study: Evaluate impact of HCV on outcome of moderate and severe TBI patients. Methods: Prospective cohort study with stratified random sample of 120 patients of moderate and severe TBI admitted in Kasr Al-Ainy hospitals in the period between February 2016 and January 2017. Screening for HCV antibodies with ELISA technique was done to detect HCV +ve patients. Assessment of case deterioration after admission, resurger, length of ICU (Intensive care unit) stay, ventilator days, mortality and GOS (Glasgow outcome score) was done. Results: Out of the 120 patients included; 11 patients were HCV +ve, while 109 patients were found negative for HCV antibody. Overall mortality was 28/120 patients. Mortality among HCV +ve patients was 7/11 patients compared with the HCV –ve patients: 21/109 patients (p=0.003). Length of ICU stay in HCV +ve patients: 8.73±4.78 days and in HCV –ve patients: 9.39±9.52 days (p=0.422). Ventilator days in HCV +ve patients were 8.69±4.12 and in HCV –ve patients: 12.51±12.31 days. Conclusion: TBI in HCV +ve patients is associated with significantly increased mortality rates and lower GOS com-pared with HCV–ve patients, which agrees with published literature in this subject. Other significant prognostic indicators were age and GCS on admission.