Objective <p>The C-PLAN index, which comprehensively considers inflammation, nutritional status, tumor grade/metabolism, and functional status, has been proven to be an effective predictor of various cancers. However, its application in patients with high-grade glioma (HGG) has not been studied. Therefore, this study aimed to analyze the impact of the C-PLAN index on the survival of HGG patients.</p> Methods <p>This study included 140 HGG patients who underwent postoperative radiotherapy/radiochemotherapy between April 2011 and May 2024. Patient medical records were retrospectively analyzed. Demographic and clinical data (IDH status, surgical procedure, histopathological type, Karnofsky Performance Status) were analyzed. Overall survival (OS) and progression-free survival (PFS) were evaluated using Kaplan–Meier survival curves and Cox regression analysis.</p> Results <p>Data from 140 HGG patients were analyzed. The median survival was 12 months (IQR 25–75: 7–21 months). In univariate analysis, IDH status (χ²(1) = 11.17, <i>p</i> &lt; 0.001), KPS score (χ²(1) = 29.57, <i>p</i> &lt; 0.001), and C-PLAN index (χ²(1) = 8.83, <i>p</i> = 0.003) were significant predictors of OS. In the multivariate analysis, IDH status (<i>p</i> = 0.003, HR = 3.23 [95% CI: 1.47–7.09]) and KPS score (<i>p</i> &lt; 0.001, HR = 2.68 [95% CI: 1.58–4.52]) remained significant predictors of OS, whereas the C-PLAN index was not significant (<i>p</i> = 0.17, HR = 0.69 [95% CI: 0.404–1.18]).</p> Discussion <p>This is the first study to investigate the impact of the C-PLAN index on overall OS in patients with HGG. The results showed that in univariate analysis, IDH status, Karnofsky Functional Status Score (KPS), and the C-PLAN index were significant predictors of OS in HGG patients. In multivariate analysis, all factors except the C-PLAN index were also significant. Further research is needed to confirm these findings.</p>