AbstractImmunogenic cell death (ICD), a unique form of cancer cell death, has therapeutic potential in anti-tumour immunotherapy. The aim of this study is to explore the predictive potential of ICD in the prognosis and immunotherapy outcomes of glioblastoma multiforme (GBM). RNA sequencing data and clinical information were downloaded from three databases. Unsupervised consistency clustering analysis was used to identify ICD-related clusters and gene clusters. Additionally, the ICD scores were determined using principal component analysis and the Boruta algorithm via dimensionality reduction techniques. Subsequently, three ICD-related clusters and three gene clusters with different prognoses were identified, with differences in specific tumour immune infiltration-related lymphocytes in these clusters. Moreover, the ICD score was well differentiated among patients with GBM, and the ICD score was considered an independent prognostic factor for patients with GBM. Furthermore, two datasets were used for the external validation of ICD scores as predictors of prognosis and immunotherapy outcomes. The validation analysis suggested that patients with high ICD scores had a worse prognosis. Additionally, a higher proportion of patients with high ICD scores were non-responsive to immunotherapy. Thus, the ICD score has the potential as a biomarker to predict the prognosis and immunotherapy outcomes of patients with GBM.