Background: According to World Health Organization (WHO) estimates, the prevalence of HCV in Egypt is 4.5% to 6.7%, which is the uppermost prevalence of HCV in the world causing a substantial burden of mortality and morbidity. Health related quality of life [HRQoL] has been assessed in diabetes, arthritis and a wide variety of cancers, Until now, there is no sufficient report about HRQoL related to direct acting antiviral agents (DAAs )on Egyptian patients with chronic HCV. This prospective cohort study aimed to assess the health related quality of life in Egyptian patients with chronic HCV treated with daclatasvir (DAC) and sofosbuvir(SOF) ± ribavirin (RBV). Methods: One hundred HCV patients were classified according to the supreme council and national committee for control of HCV (NCCVH) into two groups: Group 1 (easy to treat) included 35 patients treated with SOF+DAC for 12 weeks, and group 2 (difficult to treat) included 65 patients treated with SOF+DAC+RBV for 12 weeks. The short form 36 scale (SF-36) was used to assess the health related quality of life in two groups. Results: Sustained virological response (SVR12) in patient received DAC/SOF was 83.3 % and in patient received DAC/SOF/RBV was 100% (Total 93%). The patients reported significant improvement in all HRQoL domains after therapy, group1reported higher improvement. Conclusion: Sofosbuvir and Daclatasvir with or without ribavirin are effective in treatment of chronic HCV infections with low adverse actions and better improvement in HRQoL. Sofosbuvir and Daclatasvir have better improvement in HRQoL than Sofosbuvir and Daclatasvir plus ribavirin.