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Objective To explore new treatment methods for diffuse midline glioma (DMG), H3 K27M mutant, WHOⅣgrade. Methods A 51 years old female patient was diagnosed as DMG, H3 K27M mutant. After resection of the left frontal lobe lesion, we decided to use temozolomide super early chemotherapy treatment named START after multi⁃disciplinary team (MDT) discussion. After chemotherapy 3 weeks head MRI examination showed the lesion of tumor in the left thalamus had developed. Then conformal intensity ⁃ modulated radiotherapy combined with etoposide (VP ⁃ 16) rhythm chemotherapy was performed for intracranial lesions. The detection of whole exome sequencing (WES) indicated that the patient was sensitive to pazopanib, therefore, treatment of etoposide combined with pazopanib was carried out. Results Three months after radiotherapy, the reexamination showed that the tumor nearly achieved complete remission (CR, RANO standard). Conclusions The comprehensive treatment strategy of surgery, radiotherapy, chemotherapy and targeted therapy can improve the survival of DMG, H3 K27M mutant patients, which needs further follow⁃up observation. DOI：10.3969/j.issn.1672⁃6731.2019.12.010