Background: In Chronic Hepatitis C (CHC) disease, the role of Treg is still controversial and most studies yielded conflicting reports. Our study aimed to assess the influence of baseline Tregulatory cells on Chronic Hepatitis C (CHC) disease progression and response to treatment with direct-acting antiviral drugs (DAA).Method: This prospective cohort study included 120 CHC patients who are eligible to receive DAA treatment in National Committee for Combating Viral Hepatitis (NCCVH) at Al-AHRAR hospital, were subjected to routine laboratory investigation, pre and post-treatment polymerase chain reaction (PCR) analysis and flow cytometry analysis to reveal ratio percentages of T-regulatory cells subsets. According to response to DAA into the sustained virological response (SVR) group and Non-response (NR) group included 112 and 8 patient respectively also divided into Non-Cirrhotic and Cirrhotic groups included 103 and 17 patients respectively. Result: Comparison SVR and NR groups resulted in a significant difference between both groups with higher FOX-p3 expression among NR populations (p= 0.002). Multivariate regression analysis resulted in FOX-p3 expression as an independent factor for nonresponse to DAA treatment, there is a positive correlation between T-regulatory cells and the severity of liver disease. ROC curve analysis had shown a cut-off for FOX-p3 expression percentage (≥6.92) that can differentiate between SVR and NR groups. CD25+CD4 (P =0.002) and Fox+ve Treg (P =0.018) were higher in Cirrhotic than Non Cirrhotic group. Conclusion: T-Regulatory cell level may predict the response to DAA treatment in CHC patients.