Malignant brain tumors consist of malignancies originated primarily within the brain and the metastatic lesions disseminated from other organs. In spite of intensive studies, malignant brain tumors remain to be a medical challenge. Patient-derived organoid (PDO) can recapitulate the biological features of the primary tumor it was derived from and has emerged as a promising drug-screening model for precision therapy. Here we show a proof-of-concept based on early clinical study entailing the organoids derived from the surgically resected tumors of 26 patients with advanced malignant brain tumors enrolled during December 2020 to October 2021. The tumors included nine glioma patients, one malignant meningioma, one primary lymphoma patient, and 15 brain metastases. The primary tumor sites of the metastases included five from the lungs, three from the breasts, two from the ovaries, two from the colon, one from the testis, one of melanoma origin, and one of chondrosarcoma. Out of the 26 tissues, 13 (50%) organoids were successfully generated with a culture time of about 2 weeks. Among these patients, three were further pursued to have the organoids derived from their tumor tissues tested for the sensitivity to different therapeutic drugs in parallel to their clinical care. Our results showed that the therapeutic effects observed by the organoid models were consistent to the responses of these patients to their treatments. Our study suggests that PDO can recapitulate patient responses in the clinic with high potential of implementation in personalized medicine of malignant brain tumors.