Hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) is a novel class of orally administered medications for renal anemia in patients with end-stage renal disease (ESRD). Roxadustat, a HIF-PHI, has a structure similar to that of triiodothyronine and may work as an agonist for thyroid hormone receptor-beta in the pituitary gland and/or hypothalamus. Therefore, roxadustat may cause central hypothyroidism due to suppressing thyroid-stimulating hormone (TSH) release in the pituitary gland and/or thyrotropin-releasing hormone release in the hypothalamus. On the other hand, some symptoms of uremia and hypothyroidism, such as fatigue, anorexia, or edema, are common. Therefore, hypothyroidism might be masked by uremia in patients with ESRD. We herein report the case of a 74-year-old man with roxadustat-induced central hypothyroidism masked by uremia at the initiation of hemodialysis. After stopping roxadustat medication without thyroid hormone replacement therapy, the patient's TSH, free triiodothyronine, and free tetraiodothyronine levels returned to the normal range rapidly, and uremic-like symptoms such as anorexia and physical fatigue also gradually recovered. The number of ESRD patients undergoing treatment for renal anemia with roxadustat might increase in the future; hence, close attention to roxadustat-induced central hypothyroidism in ESRD patients with uremia at the initiation of hemodialysis is essential.