Given the potentially conflicting roles of EFEMP1 for cancer biology in general, and the importance of the EGFR signaling pathway in glioma biology, we studied its suppression of EGFR signaling pathways and tumorigenicity in different glioma cells with or without expression of EGFR, and the prognostic values in different sets of glioma patients, dichotomized based on the expression level of EGFR. Overall data from glioma experimental models and the patient prognosis values consistently demonstrates that EFEMP1 is tumor-suppressive in gliomas driven by activation of EGFR signaling pathways. This evidence concerns the gene EGFR and glioma.