Objective: To explore the effect of nursing risk management on perioperative complications and prognosis of patients with epilepsy undergoing stereo-electroencephalography (SEEG)-guided radiofrequency thermocoagulation therapy. Methods: A total of 100 patients receiving SEEG-guided radiofrequency thermocoagulation therapy in the Department of Brain Surgery of First Affiliated Hospital of Zhengzhou University from October 2018 to September 2020 were selected as research objects. According to the random number table method, they were divided into a control group and an observation group, 50 cases in each group. The control group received routine nursing management mode during the perioperative period, while the observation group received nursing risk management mode based on routine nursing during the perioperative period. The perioperative nursing quality score, operation duration, intraoperative complications, hospitalization duration, postoperative complication rate (surgery-related complications and nursing-related complications), postoperative efficacy grading (Engel grading score), and quality of life score were compared between the 2 groups. Results: The nursing quality score of the observation group was higher than that of the control group (P<0.05). The operation time and hospitalization time of the observation group were shorter than those of the control group (P<0.05). The total incidence of surgery- and nursing-related complications in the 2 groups was lower than that in the control group (P<0.05). One year after the operation, the proportion of grade I efficacy and quality of life score in the observation group were significantly better than those in the control group (P<0.05). Conclusion: Perioperative nursing risk management for epilepsy patients with SEEG-guided radiofrequency thermocoagulation therapy can significantly reduce the incidence of complications, shorten the operation time, and improve postoperative efficacy and quality of life of patients.