ABSTRACT Lung cancer is a leading cause of cancer-related deaths throughout the world. Recent genome-wide association studies and consecutive validation supported that the 5p15.33 region containing telomerase reverse transcriptase gene (TERT) and cleft lip and palate transmembrane protein 1-like (CLPTM1L) gene showed significant association with lung cancer in multiple populations. Here we studied a large Chinese Han cohort consisting of 1759 cases and 1804 controls. In the 1st stage (784 cases versus 782 controls) we genotyped 13 tag SNPs within 5p15.33 region to further investigate the association. After the 2nd stage validation (975 cases versus 1022 controls), the study clarified the association that rs2736100 of the TERT gene conferred the highest significant risk of lung cancer (P = 4 × 10(-3) in the 1st stage association, P = 4 × 10(-4) in the 2nd stage validation, and P = 1 × 10(-5), odds ratio = 1.24 in the combined population). The results provided the evidence of a cross-race susceptibility of the lung cancer locus.