Objective To explore the relationship between the SIRT1 genetic polymorphisms and chemosensitivity to platinum-based chemotherapy in lung cancer patients. Method A total of 338 lung cancer patients (184 resistant and 154 sensitive) were selected and treated by platinum-based chemotherapy in this study. All single nucleotide polymorphisms in SIRT1 gene were analyzed and four tagging SNPs were finally screened for genotyped. The odds ratios (OR) with 95％ confidence intervals (CI) were used to assess the effect of SIRT1 Genes Polymorphisms on the chemosensitivity of patients with lung cancer. Results We found a significant association of SIRT1 rs3758391 polymorphism with platinum-based chemotherapy effectiveness in lung cancer patients who were older than 60 years (OR=0.38, P=0.049). While no significant correlation was discovered between rs3740051, rs12778366 genetic polymorphism and platinum-based chemotherapy effect . Conclusion Our findings suggest that the SIRT1 rs3758391 genetic polymorphism can affect platinum-based chemotherapy sensitivity in lung cancer patients, and SIRT1 may be act as a potential biomarker on lung cancer chemotherapy response.