Objective: To analyze the effect of cone-beam computed tomography (CBCT) guided radiotherapy for malignant tumors. Methods: A total of 68 patients with malignant tumors who received radiotherapy from October 2021 to October 2022 were selected as the research objects. They were randomly divided into observation group and control group. Among them, 34 patients in the observation group received CBCT-guided radiotherapy, with a frequency of 1 time/d. 34 patients in the control group also received CBCT-guided radiotherapy, with a frequency of 1 time/3 d. The clinical effects of CBCT-guided methods were compared and analyzed. Results: The absolute values of x, y, z axis setup errors and setup expansion boundary in the observation group were lower than those in the control group (P＜0.05). The maximum irradiation dose and average irradiation dose of malignant tumor patients in the gross tumor area and planned target area in the observation group were higher than those in the control group (P＜0.05). The objective effective rate of the observation group was higher than that of the control group (P＜0.05). The quality of life scores in all fields of the observation group were higher than those of the control group (P＜0.05). Conclusion: For patients with malignant tumors, CBCT scanning and guidance before treatment can reduce the positioning error during radiotherapy. With the increase of CBCT scanning frequency, the adaptability and accuracy of radiotherapy can be better improved, the treatment effect can be ensured, and the discomfort reaction can be prevented.