Little is known about the safety and predictors of response of interferon (IFN), ribavirin (RBV), and sofosbuvir (SOF) combination in real-world settings. Hepatitis C virus (HCV) treatment decisions must depend on Real-world effectiveness data rather than clinical trails data., thus, the aim of this study is to comprehensively evaluate the safety and efficacy of this treatment in routine medical practice. A total of 105 treatment naïve patients with CHC genotype 4 with mean age 49 ± 7.26 years old of whom 62 were males and 43 were females, were treated with INF, RBV, and SOF for 12 weeks. Patients were monitored for safety and efficacy during the treatment and 12-week follow up periods. Seventy (66.67%) patients achieved a sustained virological response (SVR). The rate of SVR varied significantly by age, baseline fibrosis stage, aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum creatinine (Scr), and hemoglobin (Hb). Most adverse effects were mild to moderate in severity and were well tolerated. The overall continuance rate without dose reduction was 80.95%. one patient discontinued treatment, due to neutropenia,. Hematologic toxicity included anemia with a frequency 19.05%. The efficacy of IFN/RBV/SOF combination for treatment of Egyptian CHC patients with genotype 4 in real-world setting was less than that reported in clinical trials.