Background: Chronic inflammation was associated with the hyporesponsiveness to erythropoiesis stimulating agents (ESA) in hemodialysis (HD) patients. A rising indicator of inflammation is the platelet-to-lymphocyte ratio (PLR). Objective: The aim of the current work was to assess the role of the PLR in detection of the response to ESA in HD cases. Patients and methods: This cross-sectional study included a total of 80 patients who underwent regular HD at the Department of Internal Medicine, Zagazig University Hospitals. Patients were classified according to median value of erythropoietin hyperresponsiveness index (EHRI) into two groups: Group1; included (41 patients) with low resistance EHRI < 0.167, and Group 2: included (39 patients) with high resistance ≥ 0.167. PLR was assessed in both groups. Results: PLR best cutoff value derived from ROC curve to predict EPO resistance was ≥87.5, with specificity, and sensitivity, were 51.3%, and 56.1%, respectively. PLR had significant positive linear correlation with MCH, MCHC, PLR platelet count, serum sodium and creatinine clearance. PLR was negatively correlated with ALC, AMC, serum creatinine, potassium, and LDL cholesterol, serum iron and TIBC. However, in multivariate linear regression analysis only ALC, platelet count, TIBC and MHCH were found to be independent determents of PLR in HD case. Conclusion: Despite being a simple widely available marker of inflammation, PLR did not appear to be useful in reflecting the EHRI in CKD patients. Thus, we recommend further future multicenter and nationwide studies to stand on the suitable marker for EHRI in CKD population in Egypt.