Objective:To investigate the clinical features of Herpes simplex virus encephalitis(HSE) with cerebral hematoma as the prominent manifestation and the significanc of metagenomic next-generation sequencing (mNGS) in the diagnosis of HSE.Methods:The clinical manifestations, diagnostic process, clinical treatment and prognosis of a case of HSE with cerebral hematoma as the prominent manifestation at Shanghai Children′s Medical Center Affiliated to Shanghai Jiaotong University School of Medicine in June 2019 were retrospectively analyzed.The relevant literatures were also searched and reviewed.Results:A 4-year-old boy presented with slight fever, headache, convulsion and vomiting was considered to have intracranial space-occupying lesions and possible intratumoral hemorrhage after undergoing imaging examination at a local hospital.The patient was checked by head CT in Shanghai Children′s Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, which showed that there were many bleeding foci in the brain, indicating the possibility of complications of blood system diseases.Therefor the child was given the examination of blood routine and coagulation routine, but the results were normal, the bone marrow cytology was negative, the cerebrospinal fluid(CSF) of lumbar puncture was biochemically normal, and mNGS were 8×10 6/L.Besides, CSF smear, culture and next-generation sequencing were negative, the autoimmune encephalitis CSF testing was negative, and brain biopsy suggested inflammation.The mNGS brain tissue showed herpes simplex virus 1 was positive in two specimens, confirming the diagnosis of HSE.After 3 weeks of antiviral treatment with Aciclovir, the child′s condition improved.After a 5-month follow-up, the patient had quadriplegia and only had activities such as blinking and swallowing. Conclusions:When the intracerebral hemorrhage such as hematoma caused by encephalitis clinically can not be ruled out, the possibility of HSE should be considered, and mNGS is helpful for identifying the central ner-vous system pathogen.