Neuromyelitis optica spectrum disorder (NMOSD) is a rare immune-mediated central nervous system disease. Long-segment myelitis (>3 vertebrae), severe optic neuritis and/or intractable vomiting and hiccups (Area postrema syndrome, APS) are typical manifestations of the disease. Some cases with intractable nausea, vomiting, hiccups as the only initial symptom, result in early misdiagnosis and missed diagnosis, which delayed correct diagnosis and treatment. This article reports 2 cases of neuromyelitis optica spectrum disorders with intractable nausea, vomiting and hiccups as the initial symptom, in order to provide inspiration for the early and correct diagnosis and treatment of this disease.