Background Egypt has the highest prevalent in presence of chronic HCV infection that may lead to cirrhosis, portal hypertension, hepatocellular failure and hepatocellular carcinoma. Developing of new drugs in HCV treatment has been developed using direct acting antiviral activity. In this study we assess the safety and efficacy of a combination therapy Sofosbuvir/Simprevir in the treatment of chronic experienced HCV Method Sixty five chronic HCV patients were recruited from the outpatient clinic of Tropical Medicine Department at Fayoum public hospital.A combination of Sofosbuvir (400 mg) and Simeprevir (150 mg) was administered for those patients once daily over a period of 12 weeks. All patients have been followed up for clinical and laboratory parameters and HCV PCR to evaluate the efficacy and safety of this therapy. Result Our results show high Sustained Virologic Response rate (SVR12) which was 98.5% (64/65). Majority of patients (49.45%) reported adverse events (AEs) during treatment and most common AEs were headache, fatigue, pruritus, dizziness and photosensitivity. Conclusion On the basis of the evidence currently available, it seems fair to suggest that the combination therapy of (SMV/SOF) in the treatment of chronic HCV genotype IV experienced patient who are non-cirrhotic is safe and effective. This was evidenced by monitoring patients' clinically and using hepatic parameters after drug administration. The adverse events affected patients were mild and tolerable among patients.