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Objective. To explore the value of miR-296 and miR-517c in evaluating the prognosis of patients with glioma after radiotherapy and chemotherapy. Methods. 732 patients with glioma were selected from January 2012 to January 2018. According to the effect of postoperative chemotherapy, the patients were divided into two groups: the effective group and the ineffective group. The serum miR-296, miR-517c, and clinicopathological parameters of the two groups before chemotherapy were compared. The factors affecting the sensitivity of radiotherapy and chemotherapy and the predictive efficacy of miR-296 and miR-517c on the prognosis of patients were analyzed. Results. The expression level of miR-296 in glioma tissue was significantly correlated with tumor pathological grade and depth of invasion ( P < 0.05 ), and the expression level of miR-296 in glioma tissue was significantly correlated with tumor pathological grade ( P < 0.05 ). Logistic regression analysis showed that tumor size, WHO grade, and serum miR-296 and miR-517c levels were all factors affecting chemosensitivity ( P < 0.05 ). The sensitivity, specificity, accuracy, and AUC of serum miR-296 prediction were 76.95%, 89.64%, 85.35%, and 0.891, respectively. The sensitivity, specificity, accuracy, and AUC of serum miR-517c prediction were 72.81%, 86.50%, 82.19%, and 0.739, respectively. Conclusion. miR-296 and miR-517c are closely related to the chemosensitivity and prognosis of glioma patients. High levels of miR-296 and miR-517c can enhance chemosensitivity and serve as reliable indexes to predict the prognosis of patients with glioma.