Objective To summarize and analyze the clinical features, treatment and prognosis of children with severe anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. Methods A total of 20 cases clinical data of children patients with severe anti-NMDAR encephalitis were collected from the Department of Internal Neurology and Pediatric ICU of Children's Hospital affiliated to Chongqing Medical University from January 2014 to September 2021. The clinical features, treatment and prognosis were analyzed. Modified Rankin scale (mRS) was used to evaluate the short-term prognosis of the patients, and divided them into favourable prognosis group (mRS <2) and unfavourable prognosis group (mRS ≥2, or death), and analyze the influencing factor to prognosis. Results A total of 20 children with severe anti-NMDAR encephalitis were included, among them 11 girls and 9 boys with on-set age of (9.2±3.7) years. convulsion attack and mental behaviour disorder were the first neurological symptoms, and the main complications included consciousness disturbance (85.0%), status epilepticus (60.0%), central hypoventilation (40.0%),acute intracranial hypertension (35.0%), multiple organ dysfunction (20.0%), shock (20.0%) and rhabdomyolysis (15.0%), while no multiple organ dysfunction, shock and rhabdomyolysis occurred in favourable prognosis group. Moreover, slow wave activity was critical feature of first electroencephalography (EEG) abnormalities (95.0%), and none of the patients in favourable prognosis group had epileptiform waves and δ-brushes. The first-line immune treatment was received by all the children patients including the combination therapies of methyllprednisolone, intravenous immunoglobulin (IVIG) or plasma exchange (TPE), among them 2 cases received the second-line immunotherapy with rituximab. Glasgow coma score (GCS) scores improved after immunotherapy compared with pre-treatment. Short-term follow-up was performed for 3 months. Finally, 4 of the children patients died and 16 survived with neurological deficits, mainly including cognitive impairment (12 cases, 75.0%), language impairment (10 cases,62.5%) and motor deficits (8 cases, 50.0%), average mRS score was 2.81±1.55. The time from admission to performed the antibody testing was significantly shorter in favourable prognosis group than that in the unfavourable prognosis group. Conclusions For children patients with severe anti-NMDAR encephalitis, in addition to early testing the cerebrospinal fluid antibody, completing electroencephalogram and early initiation of immunotherapy, attention should also be paid to the management of central respiratory, cardiovascular and status epilepticus. Immunotherapy is effective in majority of the patients. However, children with severe anti-NMDAR encephalitis have a poor short-term prognosis.