Recent studies show that NOTCH3 is involved in the glioma development and it is also a prognostic factor for glioma patients. However, the gene polymorphism of NOTCH3 in gliomas prognosis remains unknown.A total of 266 patients were enrolled into this study. The NOTCH3 gene polymorphism at 3 loci, including C>T polymorphism at nucleotide 381, C>A polymorphism at 474 and G>A polymorphism at 684 were determined. All patients received the surgical treatment and/or chemotherapy and/or radiotherapy.We found that the 684G>A polymorphism affects the tumor NOTCH3 expression level and is closely associated with a higher tumor grade, poorer tumor differentiation, and karnofsky performance score in these glioma patients. More importantly, the 684G>A polymorphism is significantly associated with the prognosis of these patients regardless of their treatment manner.Our study indicates that the NOTCH3 gene 684G>A polymorphism may be used as a prognosis marker for gliomas.