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Li-Peng Jiang,1 Zhi-Tu Zhu,2 Chun-Yan He3 1Department of Radiation Oncology, 2Department of Oncology, First Affiliated Hospital of Liaoning Medical University, 3Department ofProsthodontics, Second Affiliated Hospital of Liaoning Medical University, Jinzhou, People’s Republic of China Objective: We aimed to explore the impacts of the rs776746 polymorphism in the CYP3A5 gene and smoking on the prognosis of non-small-cell lung cancer (NSCLC). Materials and methods: Our study enrolled 104 early NSCLC patients undergoing surgery and 107 advanced NSCLC patients undergoing chemotherapy, hospitalized between December 2009 and December 2012 at the First Affiliated Hospital of Liaoning Medical University. All subjects with complete follow-up data were pathologically diagnosed. The rs776746 polymorphism and different genotypes (*1/*1, *1/*3, and *3/*3) were identified by polymerase chain-reaction restriction fragment-length polymorphism. Results: Clinical response to chemotherapy in NSCLC patients with *1/*1 + *1/*3 genotypes were significantly worse than in those with the *3/*3 genotype (17.78% vs 56.45%, P