Patients with lung cancer suffer from significant psychological distress. The underlying theoretical model that may explain what predicts or mediates the degree of psychological distress has not been elucidated. To describe the incidence of psychological distress in patients with lung cancer and to test a predictive theoretical model of psychological distress based on symptom burden, type D personality, social support, and intrusive thoughts. Three hundred eighty-nine patients with stages I to IV lung cancer were recruited. Participants completed a battery of scales, including measures of psychological distress, symptom burden, type D personality, perceived social support, intrusive thoughts, and demographic and clinical characteristics. The predictive theoretical model was tested using structural equation modeling. Experiencing clinically significant psychological distress was reported by 63.75% of participants. Consistent with the social cognitive processing model, symptom burden, type D personality, social support, and intrusive thoughts all significantly and directly predicted the level of psychological distress in patients with lung cancer. Moreover, intrusive thoughts mediated the effects of type D personality and symptom burden on psychological distress; social support and symptom burden mediated the effects of type D personality on psychological distress. The majority of the participants experienced psychological distress at a clinically significant level. Intrusive thoughts and social support mediated the effects of type D personality and symptom burden on psychological distress. Patients with type D personality and symptom burden should be identified. Interventions for targeting social support and intrusive thoughts might ultimately reduce their psychological distress.