Background: Huge efforts have been made to control chronic HCV in Egypt with appearance of Direct-Acting Antivirals (DAAs) with their anticipated excellent efficacy and tolerability. Objectives: This work is evaluating the effect of DAA regimens (SOF/DAC with or without RBV) on liver biochemical profile and hematological indices during and after treatment. Methodology: 184 patients were included in this study, the patients were divided equally according to National Committee for Control of Viral Hepatitis protocol update on November 2015 (NCCVH , 2015a) into two groups treated by 2 regimens (SOF/DAC with or without RBV) according to their classification easy to treat or difficult to treat. The patients were followed up through treatment by clinical evaluation, CBC, liver functions and kidney functions after 2 weeks and 1 week (if receiving RBV) of treatment then every month till end of treatment and after 3 months of treatment stoppage. PCR for HCV RNA in week 16 [End Of Treatment (EOTR)] and 3 months after stoppage of therapy (week 24). Results: The mean age was 49 years. 58.7% were males, 41.3% were females, all of them were treatment-naïve and cirrhotic and the SVR12 rate was 94.6% without RBV and 100% with RBV regimen. Decline in ALT and AST occurred after treatment, with no change in ALB and no decrease in white blood cells in both treated groups. A rise in BIL and INR additionally, drop in hemoglopin and platelets in patients receiving (SOF/DAC/RBV) regimen .However, patients who received (SOF/DAC) showed improvement in INR and platelets. Conclusion Daclatasvir plus sofosbuvir with or without ribavirin for 12 weeks is highly effective in treatment of naïve Egyptian patients and improve hepatitis process caused by viral infection that was evidenced by decreased liver enzymes level (AST,ALT). However, Cirrhotic patients who add RBV still require careful observation as they are more susceptible for treatment related complications.