The phase I study of the tumor suppressor p53 gene therapy for advanced lung cancer was performed. A 57-year-old man with locally advanced squamous cell carcinoma at the tracheal bifurcation, clinical stage IIIB, had previously been treated by radiotherapy and chemotherapy. Because of the local recurrence, he was enrolled to the study. He was treated by a local injection of ADVEXIN once every 4 weeks for 14 times without marked adverse events, which resulted in tumor regression and relief of his symptom for a year. In conclusion, gene therapy with ADVEXIN may be an effective treatment for locally advanced non-small lung cancer.