Purpose <p>This study aims to investigate the association between sterol O-acyltransferase 1 (SOAT1) expression and patient prognosis, immune environment, and biochemical indicators in glioma.</p> Methods <p>We analyzed SOAT1 expression, immune cell infiltration, and patient prognosis using glioma cohorts from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. A retrospective cohort of 195 glioma patients who underwent surgical resection at our institution between January 2016 and December 2020 was also included. Immunohistochemical (IHC) assays were performed to evaluate the expression of SOAT1 and immune cell markers, and these results were correlated with clinical parameters and biochemical indices.</p> Results <p>SOAT1 expression in gliomas increased with tumor grade. High SOAT1 expression was associated with worse prognosis, and this association remained significant in multivariable Cox models. Immune infiltration analysis revealed a significant positive association between SOAT1 expression and multiple tumor-infiltrating immune cells, particularly monocytes-macrophages and neutrophils. Furthermore, patients with high SOAT1 expression exhibited elevated circulating neutrophils, neutrophil-to-lymphocyte ratio (NLR), (white blood cell-neutrophil)-to-lymphocyte ratio (dNLR) and systemic immune-inflammation index (SII), accompanied by decreased lymphocyte and monocyte counts. Additionally, high SOAT1 expression was associated with reduced serum sodium (Na⁺) and chloride (Cl⁻) levels, as well as increased levels of bilirubin.</p> Conclusion <p>SOAT1 expression is closely associated with glioma prognosis, immune cell infiltration, systemic inflammatory and biochemical indicators. These findings offer novel insights into the role of SOAT1 in glioma and its broader implications for systemic immune and biochemical alterations, providing a foundation for future research into potential therapeutic targets and prognostic biomarkers.</p>