A 72-year-old male on maintenance hemodialysis presented with rare and severe hyporesponsiveness to erythropoiesis-stimulating agents (ESAs). Despite a weekly administration of 24,000 IU of recombinant human erythropoietin (rhuEPO), in line with the patient’s weight of 62 kg, he continued to require frequent blood transfusions, and his hemoglobin (Hb) levels plummeted precipitously over a brief period. The etiology of his refractory anemia was elusive. The patient presented with a high reticulocyte count, and no signs of iron deficiency, impaired iron utilization, overt infection, secondary hyperparathyroidism, hemolytic anemia, or significant gastrointestinal bleeding were observed. Interestingly, upon initiation of treatment with roxadustat, a marked reduction in transfusion frequency and iron supplementation dosage was observed, concurrent with a substantial elevation in hemoglobin levels. The efficacy of roxadustat in this patient suggested that it would be an alternative therapy for those with ESA hyporesponsiveness in renal anemia. Clearly, as the mechanistically new type of drug for renal anemia, it is worthwhile to further understand its unique role in the treatment of renal anemia.