BACKGROUND AND STUDY AIMS: Hepatitis C virus (HCV) infection is a significant problem in Egypt, as it is associated with various hematological disorders, both benign and malignant. In Egypt, direct-acting antivirals (DAAs) serve as the principal therapy for HCV to achieve a sustained virological response (SVR). This study investigated the effects of sofosbuvir (SOF) and daclatasvir (DCV) on HCV patients with benign blood index abnormalities and examined the correlation between these abnormalities and SVR. PATIENTS AND METHODS: Data were obtained from 59,069 enrolled patients who were treatment-naïve and met the eligibility criteria for therapy as per the standards of Egypt's National Committee for Control of Viral Hepatitis (NCCVH). The patients adhered to the SOF and DCV therapy protocol. RESULTS: The predominant hematological abnormality was thrombocytopenia, followed by leukopenia and anemia. Non-SVR was significantly correlated with the existence of one or more baseline cytopenias. The primary predictors of treatment failure were male gender, elevated Fib-4 score, and baseline thrombocytopenia. Despite the low incidence of cytopenia among patients after therapy, non-SVR was seen in instances of anemia. CONCLUSION: Hematological problems often occur in HCV patients both before and after SOF and DCV treatment. Treatment failure was associated with the presence of one or more baseline cytopenias, as well as the development of anemia during treatment. Nonetheless, SOF and DCV are still safe to be used in the presence of cytopenia.