Gliomas are the most common and malignant intracranial tumors. The standard therapy is surgical resection combined with radiotherapy and chemotherapy. However, the emergence of radioresistance and chemoresistance, which largely due to DNA damage repair, limits the therapeutic efficacy. Therefore, we identified a high-efficiency DNA damage repair-related risk signature as a predictor for prognosis in lower-grade glioma. The signature was developed and validated in two independent datasets of the Chinese Glioma Genome Atlas (CGGA, 172 samples) and The Cancer Genome Atlas (TCGA, 451 samples). The time-dependent ROC Curve, Cox regression, Nomogram and Kaplan-Meier analyses were performed to evaluate the prognostic performance of the risk signature. The Metascape and immunohistochemistry staining were performed to reveal the potential biological mechanism. Graphpad Prism, SPSS and R language were used for statistical analysis and graphical work. This signature could distinguish the prognosis of patients, and patients with high risk score exhibited short survival time. The time-dependent ROC Curve, Cox regression and Nomogram model indicated the independent prognostic performance and high prognostic accuracy of the signature for survival. Combined with the IDH mutation status, this risk signature could further subdivide patients with distinct survival. Functional analysis of associated genes revealed signature-related biological process of cell cycle and DNA repair. These mechanisms were confirmed in patient samples. The DNA damage repair-related signature was an independent and powerful prognostic biomarker in lower-grade glioma. The signature may potentially improve risk stratification of patients and provide a more accurate assessment of personalized treatment in clinic. Copyright ©2019, American Association for Cancer Research.