Background and Aim: Anemia is a common and serious complication of chronic kidney disease (CKD). Despite the use of erythropoietin, anemia of CKD can be resistant to therapy. Hepcidin is the main iron regulatory hormone; increased hepcidin production during chronic inflammation interferes with iron absorption, prevents iron recycling leading to hypoferremia and iron-restricted erythropoiesis. Our study aims to evaluate the role of serum hepcidin in predicting the response to erythropoietin (EPO) therapy in children with CKD on regular hemodialysis. Subjects and methods: a cross sectional comparative study included 40 children with CKD on regular hemodialysis who received EPO therapy for at least 3 months and 40 age and sex matched healthy children. Assessment of anemia and iron profile before and after 3 months of EPO therapy and was correlated to the serum level of hepcidin. Results: in comparison to healthy controls, CKD children have significant anemia and high hepcidin level. CKD children have CKD children with high hepcidin level have significant lower hemoglobin and impaired response to EPO therapy in comparison to those with normal hepcidin level (P-value <0.005). There was significant negative correlation between serum hepcidin level and HB, HCT and iron level in children with CKD. Conclusion: children with CKD on regular dialysis have higher hepcidin level that interferes with the response of anemia to EPO therapy suggesting functional defect in iron utilization among those children