Inflammation plays an important role in proliferation, migration, and invasion of tumor cells; therefore, many research has been done to investigate inflammation parameters including systemic immune-inflammatory index (SII). Dexamethasone, a strong anti-inflammatory, is still widely used as the main treatment in vasogenic edema. High-dose administration (16 mg/day) is recommended in patients with brain tumors with increased intracranial pressure. We performed this retrospective study to determine SII profile, dexamethasone use, and the effect of high-dose dexamethasone on SII in patients with brain tumors. We performed a retrospective study on patients with brain tumors in 2022-2023 period who were treated with intravenous high-dose dexamethasone. Patient demographics, clinical characteristics of the brain tumor, concurrent infection, as well as dexamethasone dose and duration were recorded. Platelet, neutrophil, and lymphocyte count obtained prior to dexamethasone administration, and on the fifth to seventh day were also collected. SII was calculated by the following formula: neutrophil × platelet counts/lymphocyte. Data were then analyzed using Microsoft Excel 2019 and SPSS 29.0.2.0. We enrolled 56 patients with brain tumors, age 47±13.5 years, 78.6% were female, 69.6% had malignant brain tumors (brain metastases and high-grade primary brain tumors) and 26.8% had concurrent infection. High-dose dexamethasone was administered with average dose of 16.8±3.3 mg/day for average duration of 4.8±1.8 days. SII was significantly higher in malignant compared to benign brain tumors both in prior and after dexamethasone administration (P=0.02, P=0.01). SII was significantly higher in metastasis brain tumor compared to primary brain tumor (P=0.005). High-dose dexamethasone significantly increased SII and decreased lymphocyte count (P=0.006, P=0.04). SII was found higher in malignant brain tumor and brain metastasis. High-dose dexamethasone was administered with average dose of 16.81±3.37 mg/day for average duration of 4.78±1.84 days. SII was found to be higher after high-dose dexamethasone, due to a decrease of lymphocyte counts in peripheral blood.