Hepatitis C virus (HCV) infection is a major worldwide health issue, and the introduction of direct-acting antivirals (DAAs) has greatly transformed its treatment. However, it is important to note that not all patients experience sustained virologic response (SVR) after undergoing DAA medication. The study aims to provide significant insights into the role of IL-10 in the immune response to HCV infection and its correlation with treatment success. The Egyptian National Committee for Control of Viral Hepatitis (NCCVH) recommended that 4300 patients receive the new DAA therapy for HCV infection treatment. We subjected all patients to a liver profile, creatinine, complete blood count, prothrombin time, serum Alpha-Fetoprotein (AFP), RT-PCR for HCV diagnosis, and determination of serum human IL-10 using a commercial ELISA kit. Non-responder patients were associated with significantly high levels of alanine (ALT) and aspartate aminotransferase (AST), ALP, and total bilirubin. Conversely, they had significantly decreased levels of albumin and platelet count. Moreover, non-responder patients had significantly high values of two common fibrosis markers fibrosis-4 score (FIB-4) and AST to platelet ratio index (APRI). There was no association (P >0.05) between treatment failure and IL-10 (18.99±7.24 vs. 18.82±4.19 pg/mL for non-responder and responder patients, respectively). The ROC revealed that IL-10 has an AUC of 0.0.546 for separating non-responder patients with poor sensitivity and specificity values. Regardless of DAA HCV treatment, the serum level of IL-10 doesn't differ significantly. DAA therapy alone may not result in substantial variations in IL-10 levels between responders and non-responders.