Abstract: Objective To investigate and analyze the clinical features of postoperative seizures of glioma patients and the expression of high mobility group box B1 protein in glioma tissues. Methods One hundred and one cases of glioma with recurrent epileptic seizure, 70 cases of glioma without seizure, 70 cases of epileptic seizure without glioma and 50 cases of cranial decompression in our hospital between January 2013 and June 2017 were enrolled into this study. The clinical pathological factors that affected the expression of HMGB in the glioma patients with epileptic seizure were explored. The expression of HMGB1 in the brain tissues were compared among the four groups. The effects of pathological grade of glioma and the accompanied with epilepsy on the expression of HMGB1 were analyzed. Results The expression of HMGB1 in epileptogenic focus tissues was not obviously related to the gender, age and location of the epileptogenic foci in the Glioma patients with epileptic seizure (all P > 0.05), however, it significantly related to the pathological grade of glioma, episode time and frequency (all P < 0.05). The positive expression of HMGB1 in the glioma group with epilepsy was higher than that in other three groups. In the patients with lower pathological grade glioma, the expression of HMGB1 in glioma patients with epileptic seizure was higher than that in the glioma patients without seizure, the difference was significant (P < 0.05). In the patients with higher pathological grade glioma, there was no significant difference in the expression of HMGB1 between glioma patients with epileptic seizure and without seizure (P > 0.05). Conclusion The expression of HMGB1 in glioma patients with recurrent epileptic seizure is high, which is associated with the histological grade, episode time and seizure frequency. The high expression of HMGB1 may be related to epilepsy, its clinical research value should be paid.