: Direct acting antiviral agents will change the shape of the future of liver diseases especially in countries where hepatitis C virus (HCV) infection is the main cause of liver pathology. Sofosbuvir, an approved DAAs, has been incorporated into several IFN-free regimen. Some clinicians observed occurrence of HCC with initiation of DAA in cirrhotic patients, so, the clinical history and data of the reported HCC-developed patients need to be analyzed carefully before any conclusive comments. Aim We evaluated the efficacy and safety and searched for development of new hepatocellular carcinoma in Egyptian cirrhotic patients with chronic hepatitis C who are treated by a sofosbuvir-based regimen. Methods Treatment-naïve or treatment-experienced patients with genotype 4 HCV (+) advanced liver disease, who had been treated with Sofosbuvir- containing regimens (n = 200) were randomly assigned to receive either 24 weeks of sofosbuvir and ribavirin daily or 12 weeks of sofosbuvir, daclatasvir and ribavirin. Results SVR12 rates were 95% (114/120) with 24 weeks of sofosbuvir and ribavirin and 97.5% (78/80) with 12 weeks of sofosbuvir, daclatasvir and ribavirin therapy. The most common adverse events in both groups were headache, insomnia, diarrhea and fatigue. No patients had adverse events leading to dose modification, interruption, or discontinuation of sofosbuvir. Hepatocellular carcinoma was detected in one patient. Conclusion sofosbuvir-containing regimen is promising and safe.