Objective: To evaluate the degree of psychological distress and analyze the influential factors of cancer patients receiving radiotherapy, aiming to provide theoretical basis for individualized psychological interventions. Methods: A cross-sectional survey of 157 cancer patients treated with radiotherapy in Sun Yat-sen Memorial Hospital of Sun Yat-sen University in the previous year was conducted in terms of data collection and mean score of NCCN distress thermometer by using the convenience sampling method. Tumor types included nasopharyngeal cancer, breast cancer and cervical cancer, etc. The influential factors were analyzed by using logistic regression method. Results: The mean score of NCCN distress thermometer in 157 cancer patients was 4.07±0.19. Among them, 87 cases (55.41%) experienced significant psychological distress (NCCN distress thermometer score≥4). The main influential factors of psychological distress consisted of depression, loneliness, fear, appearance changes, urination changes, nausea, poor appetite, eating trouble, diarrhoea, constipation, pain and radiodermatitis. Logistic regression analysis demonstrated that nausea and urination changes were the independent influential factors of psychological distress. Conclusions Over half of cancer patients undergoing radiotherapy present with evident psychological distress. Somatic problems and emotional situations are the main factors of psychological pain. Consequently, it is highly necessary to emphasize the psychological health and actively resolve the somatic and emotional symptoms of cancer patients receiving radiotherapy.