Objective To explore the expression and prognostic value of CD151 in gliomas and reveal the functional role of CD151 in gliomas. Methods The expression level, diagnostic efficacy, prognostic value, clinical significance and immunotherapeutic efficacy of CD151 in gliomas were investigated using the TCGA, CGGA, GSE16011, GSE43378, GSE4412 and PRJNA482620 cohorts. U87 was transfected with lentivirus expressing recombinant small hairpin ribonucleic acid (shRNA), and the proliferative capacity of the cells was examined by CCK8, plate clone formation, and cell cycle assays. Cell migration and invasion abilities were detected using scratch assay and Transwell assay.Results CD151 expression in glioma tissues was significantly higher than that in normal brain tissues, and the higher the WHO stage, the higher the CD151 expression. The overall survival of glioma patients was significantly shorter in the high-expression group compared with the low-expression group of CD151. CD151 was correlated with age, tissue typing, molecular typing, and therapeutic outcome of glioma patients. High CD151 expression was associated with immunosuppressive status and low remission rates with immunotherapy. Compared with the control group, the proliferative vigor, number of cell clones, rate of scratch healing, and number of membrane-penetrating cells were significantly reduced in the shRNA-CD151 group. Cell cycle assays confirmed the reduced number of G2/M phase cells in CD151-reduced cells. Conclusion CD151 is abnormally highly expressed in gliomas, and its elevated expression correlates with low therapeutic remission and poor prognosis in patients. Knockdown of CD151 expression significantly inhibites the proliferation, migration and invasion of glioma cells. Therefore, CD151 is expected to be a potential molecular marker and therapeutic target for glioma