Objective To investigate the expression of the transcription factor CUX-1 in glioma and its significance for the clinicopathological parameters and prognosis of patients.Methods TCGA database was used to perform a bioinformatic analysis on the differential expression of CUX-1 in tumor and normal brain tissue and its effect on the overall survival (OS) of patients. Western blot and immunohistochemistry were used to determine CUX-1 expression in different grades of gliomas and analyze its effects on the clinicopathological parameters and prognosis of patients.Results The bioinformatic analysis indicated that CUX-1 expression was significantly increased in glioma and high CUX-1 expression significantly shortened the survival of patients. The results of Western blot and immunohistochemistry indicated that CUX-1 expression was up-regulated with increasing WHO grade of tumor (P<0.05) and was significantly correlated with the WHO grade of glioma and the levels of proliferation indices (Ki67 and P53mut) (P<0.05). The Kaplan-Meier analysis suggested that patients with low CUX-1 expression had significantly longer overall survival than those with high CUX-1 expression (P<0.01).Conclusions CUX-1 expression is significantly up-regulated in glioma and is closely associated with tumor proliferation. Meanwhile, high CUX-1 expression suggests poor prognosis of the patient. In summary, CUX-1 holds promise as a prognostic molecular biomarker and potential therapeutic target for glioma.