Background: Medical treatment of decompensated cirrhosis due to hepatitis C virus (HCV) remains a clinical challenge even in the era of direct-acting antiviral drugs (DAAs). We evaluated the efficacy and safety of DAAs in the management of HCV-related decompensated cirrhosis. Objective: The current study aimed to evaluate the efficacy and safety of DAAs in managing HCV patients with decompensated cirrhosis and the impact of achieving sustained virological response on improving the quality of life, short term survival and if viral eradication would step down CTP score. Patients and Methods: The study included a treatment group I (n = 25) composed of HCV patients with decompensated cirrhosis Child B and group II (n = 22) with decompensated cirrhosis Child C. both groups received DAAs (sofosbuvir 400 mg, daclatasvir 60 mg) plus ribavirin as tolerated for 3 months and follow-up was done for 6 months. Results: In both treated groups, there were improvements in platelet count, albumin, Child-Torcout-Pugh (CTP) (p = 0.001) and a significant reduction in the frequency of hepatic encephalopathy (HE). Also, there was improvement in quality of life of both treated groups. Conclusion: Treatment of HCV with decompensated cirrhosis with DAAS had improved CTP score, quality of life and survival.