Abstract: Patients with locally advanced non-small cell lung cancer are high-risk populations who usually suffer from severe or mixed infections because of their complex body conditions.The main causes of severe infections in patients with high risk factors include smoking history, diabetes, chronic obstructive pulmonary disease, and pulmonary congestion and swelling caused by the decline in lung self-cleaning functions.Other possible causes include surgical operations, radiotherapy, chemotherapy, and other treatments and medications that can result in the immunosuppressive state.Lung cancers complicated with severe infections have diverse clinical manifestations, result in complex mechanisms and rapid disease progression, and have poor prognosis.The lack of an effective evaluation system for clinical treatment and the changes in the clinical and radiographic fields are not synchronous with the wide variety of disease diiferentiation.The current report presents one case of a locally advanced non-small cell lung cancer complicated with a severe mixed infection, which was treated with the multimodality treatment.The developed comprehensive chemotherapy treatment for the severe mixed pulmonary infection was found effective.These results can be used for the differential diagnosis of lung cancer complicated with severe mixed infections and for the development of specific treatments.