Background and aim There have been significant advancements during the last few years, with large numbers of ongoing trials with various direct-acting antivirals (DAA) showing high potency against the hepatitis C virus (HCV). The aim was to show the effectiveness and side effects of Sofosbuvir-based therapy in treating HCV genotype 4 in Egyptian patients and compare its results with the international results. Methods The study included 740 patients with chronic HCV. The study population consisted of three groups: Group (1): included 240 patients treated with sofosbuvir 400 mg plus Peginterferon α2a and weight-based ribavirin for 12 weeks. Group (2): had 250 patients treated with sofosbuvir 400 mg and weight-based ribavirin for 24 weeks.  Group (3): involved 250 patients treated with sofosbuvir 400 mg and simeprevir 150 mg once daily for 12weeks. Results Sustained virological response (SVR) occurred in 83.3% of the triple therapy group. In the dual therapy group, SVR occurred in 64% of patients. In the Simeprevir-Sofosbuvir group, SVR was achieved in 96% of patients, with statistically significant differences among the studied groups (p=0.015). Multivariate logistic regression analysis showed that treatment with simeprevir and sofosbuvir was associated with higher rates of SVR with an odds ratio of 12.5. Serum creatinine shows a negative correlation with an odds ratio of 3.1; MELD score showed a negative correlation with an odds ratio of 1.5. Conclusion Sofosbuvir-based therapy has satisfactory results for the treatment of hepatitis C virus genotype 4 with lesser complications