Introduction: According to the World Health Organization (WHO) in 2020, brain and central nervous system (CNS) cancers account for 2% of all newly diagnosed cancers in the world and 1.5% in Mongolia. Approximately 85-90% of all brain and other CNS tumors were diagnosed primary brain tumor. In 2019, the average 5 year survival probability was 50% for other cancers and 11% for the primary brain tumors. There were 28 patients with primary brain tumor and 33 relatively healthy individuals in our study. Goal: To study the diagnostic value of serum aquaporin-4 and glial fibrous acidic protein in the diagnosis of primary brain cancer Material and Methods: The Department of Neurosurgery at Third central hospital included 28 patients with primary brain cancer and 33 relatively healthy people. The study was conducted under the permission of the Medical Ethics Review Committee of the Ministry of Health on June 19, 2019 №119. Serum aquaporin-4 and glial fibrous acidic protein content was determined by the ELISA kits method using the human aquaporin-4 and glial fibrous acid protein test kit of the Chinese company “Sanlong”. The level is assumed to be true if the p value is less than 0.05. Results Mean age of the all participants was 42.9±16.5, 64% female and 36% male. Serum aquaporin-4 protein levels were 175.71±13.3 pg/ml and serum glial fibrilliary acidic protein levels were 2.682±0.218 ng/ml in patient with primary brain tumor. Serum aquaporin-4 protein and glial fibrilliary acidic protein levels were statistically significant high (p<0.001) in patient with primary brain tumor. Serum aquaporin-4 protein and glial fibrilliary acidic protein level differences were statistically significant (p<0.05) in benign and malignant tumor. There was no statistically significant correlation between serum aquaporin-4 and glial fibrillary acidic protein level and primary brain tumor grade.