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Background FOXP2 is an essential transcription factor for the development of language. It has also a high expression in some neosplasm, with a differential role as a prognostic biomarker. However, the role of FOXP2 in glioblastoma (GBM) has not been studied until now. AIM To study the role of FOXP2 as a prognostic biomarker in GBM. METHODS This is a retrospective observational case series study in which the expression of FOXP2 has been analyzed at the protein level (immunochemistry, in probes from patients treated in our Center) and at the level of mRNA (RNAseq, in a cohort of GBM patients from The Cancer Genome Atlas [TCGA] database). The expression of some target genes of FOXP2 (RNAseq) has also been studied in the TCGA cohort. Survival analysis using Log-Rank test and COX regression (uni- and multivariate) have been used. The analysis included also other molecular and clinical features of interest in GBM. RESULTS At protein level, FOXP2 was expressed in more than 90% of patients, with a mean positivity of 28.33% (SD=32.29). At mRNA level, FOXP2 was expressed in 79% of patients, with a mean expression of 29.72 RPKM (SD=63.77). Patients with a high expression of FOXP2 at protein level showed a worse prognosis than those patients with low expression in both, progression free survival (HR=1.711; p=.034) and overall survival (HR=1.809; p=.014). These associations maintained their significance in multivariate analysis. Nevertheless, no prognostic association was found with mRNA FOXP2 expression. Interestingly, FOXP2 target genes did not show the expected regulation described in previous works. Some of these genes has been involved in oncogenesis. CONCLUSION FOXP2 is expressed in many GBM patients. Higher expression of FOXP2 protein may be associated with a worse prognosis, but this has not been confirmed at mRNA. Furthermore, a dysregulation of FOXP2 function may be present in tumoral cells.