Introduction: Survivin is an apoptotic inhibitor, involves in regulation of apoptosis and cell cycle progression, and its polymorphisms may influence the development and progression of cancer. This study evaluated the impact of the survivin gene polymorphisms on survival of non-small cell lung cancer (NSCLC) patients. Methods: In this case-cohort follow-up study, a total of 568 NSCLC patients were investigated and 12 single nucleotide polymorphisms in survivin gene were genotyped by using the Illumina GoldenGate platform. Results: During the maximum of 72 months of follow-up, 314 (55.11%) deaths were observed. After adjusting for age, gender, smoking status, histology, stage, surgical operation, and chemotherapy or radiotherapy status, Cox hazard proportional model suggested that four single nucleotide polymorphisms had statistically significant impacts on NSCLC survival (rs3764383, AG/GG versus AA, hazard ratio [HR] = 0.78, 95% confidence interval [CI]: 0.62-0.99; rs8073069, GG versus CG/CC, HR = 1.76, 95% CI: 1.16-2.67; rs4789551, GG versus AG/AA, HR = 2.04, 95% CI: 1.08-3.86; rs1042489, GG versus AG/AA, HR = 1.37, 95% CI: 1.03-1.83). Further combined analysis showed that the high risk group (3-4 unfavorable loci) presented a 1.84-fold (95% CI: 1.22-2.77) increased risk compared with low risk group (0-2 unfavorable loci). Among 185 stage III to IV patients who received only chemotherapy, only the potentially functional rs8073069 still had a significantly increased risk on the prognosis of NSCLC (GG versus CG/CC, HR = 2.06, 95% CI: 1.10-3.87). Conclusions: Our results suggest that polymorphisms in survivin may be a genetic modifier for NSCLC prognosis in this Chinese population. © 2010 by the International Association for the Study of Lung Cancer.