ABSTRACT. Genome-wide association studies in several ethnic groups have reported that polymorphisms of the telomerase reverse transcriptase (TERT) and cleft lip and palate transmembrane 1-like (CLPTM1L) genes, located on 5p15.33, are associated with susceptibility to lung cancer. However, whether genetic variants of TERT-CLPTM1L are associated with an increased risk of lung cancer in the Chinese Han population is unknown. This study examined associations between five single nucleotide polymorphisms (SNPs) of TERT-CLPTM1L (rs402710, rs401681, rs465498, rs4975616, and rs2736100) and lung cancer in a Chinese Han population in the Hubei Province. The five SNPs were detected using the Sequenom MassArray ® iPLEX System in 304 lung cancer patients and 319 controls. Of the five SNPs, rs4975616 did not conform to Hardy-Weinberg equilibrium in the controls. Only rs2736100 was significantly (P = 0.034) associated with an increased risk of lung cancer. In the linkage disequilibrium analyses, a block of strong linkage disequilibrium was observed between rs401681 and (2015) rs465498 (D′ = 0.986; r 2 = 0.546). No linkage disequilibrium between rs2736100 and the other three SNPs was found. In the haplotype analyses, the frequencies of the TTCT haplotype in rs402710, rs401681, rs465498, and rs2736100 differed significantly between case and control subjects (odds ratio = 0.56; 95% confidence interval, 0.36-0.88; P = 0.012). The results of this study suggested that rs2736100 on TERT-CLPTM1L indicates a poor prognosis for lung cancer in the Chinese Han population.