Introduction: Chronic renal failure CRF is a widespread, irreversible disease that develops gradually and is classified into five stages depending on the glomerular filtration rate GFR. Anemia is a considerable complication of CRF that becomes serious as GFR decreases, erythropoietin-stimulating agent ESA is used for treating anemia, but the resistance to it stands against its goal in many patients. Studying the genetic polymorphism in one of the erythropoietin-activated pathway store-operated calcium channels SOCs gene is a trial for investigating the cause of resistance. Method: In this study, 174 subjects were included. Among 112 hemodialysis patients with CRF, 54.5% were non-responders, and the enrolled participants ranged from 20 to 79 years; a single nucleotide polymorphism in the ORAI1 gene was selected. Genotyping was done using an allele-specific polymerase chain reaction technique, and the data was analyzed through the Statistical Package for the Social Sciences. Results: The results showed that hemoglobin levels differ significantly between the genetic groups, while erythropoietin levels showed no significant variation. Conclusion: ORAI1 genetic polymorphism has no significant role in erythropoietin resistance in Iraqi hemodialysis patients with CRF, but this genetic variation significantly affects hemoglobin levels, depending on this study.