Background and study aim: Hepatitis C is the most pressing public health challenge in Egypt with variable prevalence rates among different age groups. This study aimed to detect the efficacy and adverse effects of sofosbuvir plus daclatasvir therapy in treatment of chronic HCV patients in Sharkia governorate. Patients and Methods: One hundred and ten patients were included in this study, divided into 4 groups; group I: 55 treatment naïve patients receiving (sofosbuvir  + daclatasvir) for 12 weeks, group II: 36 treatment naïve patients receiving (sofosbuvir + daclatasvir +ribavirin) for 12 weeks, Group III: 9 treatment experienced patients receiving (sofosbuvir + daclatasvir + ribavirin) for Session [UserIDID] weeks and Group IV: 10 chronic HCV patients not receiving anti-viral therapy. Patients were followed by clinical and laboratory evaluation monthly during treatment and for 3 months after end of treatment. In addition, the virological response and adverse effects were reported. Results: The rate of SVR response was equal in the three treated groups. There was statistically significant increase in nausea and headache in groups I and II while arthralgia, myalgia and fatigue were more frequent in group I. There was also statistically significant improvement in Child score among treated cirrhotic patients after treatment. Conclusion: Daclatasvir plus sofosbuvir with or without ribavirin for 12 or Session [UserIDID] weeks is highly effective in treatment of naïve or experienced Egyptian HCV patients in Sharkia governorate. This combination is well tolerated in both cirrhotic and non-cirrhotic patients with mild adverse effects.