Although hemangioendothelioma (HHE) is a commonly encountered hepatic tumor during infancy, HHE-related hypothyroidism is rare. We present a patient who developed HHE-related hypothyroidism during the neonatal period and showed marked improvement in hypothyroidism by regression of HHE. A 28-day-old boy with TSH level of 77 mIU/mL on neonatal screening and diagnosed as congenital hypothyroidism was started on L-thyroxine (L-T4) (11 μg/kg/day) therapy on the 21(th) day of life. On physical examination, the liver was palpable 5 cm below the right costal margin, and the thyroid gland was nonpalpable. Thyroid ultrasonography was normal. Although L-T4 dose was increased to 15 μg/kg/day, TSH was not suppressed and free T3 level remained low. HHE in both lobes of the liver was detected by abdominal ultrasonography and magnetic resonance imaging. Treatment was started with prednisolone 2 mg/kg/day and alpha-interferon 3 million U/m(2)/3 times per week. Thyroid dysfunction was thought to be due to type 3 iodothyronine deiodinase activity expressed by HHE. L-T4 therapy was changed to Bitiron® tablet, which includes both T4 and T3, and euthyroidism was attained within 1 month. Thyroid hormone requirement was reduced and treatment was discontinued after regression of the HHE. At the most recent visit, the patient was 21 months old and off treatment. His growth and neurological development were normal for age and he was euthyroid. HHE should be considered in cases with severe hypothyroidism resistant to high-dose thyroid hormone replacement. The treatment of HHE in combination with T4 and T3 therapy results in euthyroidism.