Background: A number of genome-wide association (GWA) studies have reported two SNPs, rs2736100 and rs402710 at 15p15.33 containing TERT and CLPTM1L genes to contribute to lung cancer susceptibility. However, the causative functional SNP(s) for the association as well as the biologic mechanism underlying the association remains unknown. Materials and Methods: Potentially functional SNPs in the TERT/CLPTM1L locus were selected from the NIEHS website and evaluated the effects of the SNPs on lung cancer susceptibility and on survival outcomes, in a case-control study (1094 cases and 1098 controls) and in a study of 340 patients with early stage surgically resected NSCLC, respectively. The association of the SNPs with telomere length and telomerase activity was evaluated. The functional effect of SNPs was evaluated by promoter assay and EMSA. Results: Three SNPs, rs2853669 (-244 T＞C), rs2736098 (A305A), and rs2736100 (IVS2 T＞G) were significantly associated with the risk of lung cancer. Only the rs2853669 was significantly associated with prognosis of lung cancer. The rs2853669 had a significant association with telomere length and telomerase activity. Promoter assay and EMSA revealed that the rs2853669 lead to change promoter activity and c-Myc binding efficiency to TERT promoter. Conclusions: Our results suggest that the rs2853669 is the causative functional SNP for the association of 15p13.33 with lung cancer observed in GWA studies and that this SNP changes TERT expression and telomere length, thereby contributing to lung cancer susceptibility and prognosis.