Objective To investigate the difference of survival time and its related factors in non-small cell lung cancer patients with brain metastases and negative driver gene treated by radiotherapy and gamma knife combined with radiotherapy. Methods A total of 170 patients with brain metastases from non-small cell lung cancer with negative driver gene were selected retrospectively as the research subjects from January 2018 to January 2021 in Qilu Hospital of Shandong University Eastern Court. According to different treatment methods, they were divided into radiotherapy group(135 cases) and gamma knife combined radiotherapy group (35 cases). The difference in survival and related influencing factors were compared between the two groups. Results There was no significant difference between the two groups in overall survival time (P>0.05). Cox regression analysis showed that Karnofsky score ≥70 points （β=-0.963, HR=0.382, 95%CI=0.205-0.710） and maximum lesion volume <10 ml （β=-0.567, HR=0.567, 95%CI=0.335-0.962） in the radio therapy group were protective factors for the overall survival of patients (P<0.05). In the gamma knife combined with radiotherapy group, the control of primary tumor （β=-2.414, HR=0.089, 95%CI=0.021-0.381） and the number of metastatic lesions less than 4 （β=-2.730, HR=0.065, 95%CI=0.013-0.323） were the protective factors for the overall survivnl of patients (P<0.05). Conclusion Non-small cell lung cancer patients and negative driver gene received radiotherapy alone or gamma knife combined with radiotherapy, and there was no difference in survival time between the two groups. When the primary focus is not effectively controlled or the number of metastatic focus was more than 4, the survival time of patients treated with radiotherapy alone was longer.