Background: Clotting fibrinogen-like protein 2 (FGL2) is a member of the fibrinogen-related protein family, FGL2 accelerated the development of glioblastoma multiforme (GBM) by triggering several immunosuppressive processes. Objective: The current study intended to understand FGL2 expression and prognostic significance in patients with high-grade gliomas. Patients and Methods: In our study, we examined 60 samples from patients with high-grade gliomas who received temozolomide and radiation at the same time from October 2019 to December 2020, as well as a one-year follow-up. FGL2 immunohistochemistry is used to measure the amount of FGL2. Result: Those who had progressed had considerably greater FGL2 percentages (76.54 18.52 vs. 56.17 33.41(%); P=0.04) than patients who had not progressed. Patients whose illness was progressing had higher levels of FGL2. Negative FGL2 expression was present in seven (14.9%) individuals who had no illness progression. Patients with negative FGL2 and mild intensity had the highest disease-free progression (DFP) (25 months), whereas those with strong intensity had the lowest (14 months). Among patients who passed away, the percentage of FGL2 was substantially greater (64.86 31.58 vs. 54.16 31.71(%); P 0.03). Patients with negative FGL2 and mild intensity had the highest DFP, whereas those with strong intensity had the lowest overall survival (19 months) (27 and 26 months, respectively). FGL2 at a cut-off point > 70% had 67% sensitivity and 61% specificity with an overall accuracy of 63.4% for predicting death in individuals with high-grade glioma. Conclusion: FGL2 expression in high-grade glioma patients can be utilized as a prognostic indicator, though further research is needed to fully understand the predictive usefulness.