Ewing’s Sacroma (EWS) is a carcinogenic bone tumor which is predominantly occurred in young adults. EWS RNA binding protein 1 (Ewsr1) protein is well-known as a multifunctional protein and its epigenetic signatures contribute to the pathogenesis of various human disease such as neurodegenerative disorders, skin development, or tumorigenic process. However, the specific cellular function and physiological characteristics of Ewsr1 are still ambiguous. In this study, therefore, we applied TMT-labeled quantitative mass spectrometry-based proteomic approach to investigate the global proteome changes of brain tissue between Ewsr1 knock-out (KO) and wild type (WT) mice (n=3, each).