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Telomerase reverse transcriptase (TERT) is the catalytic component of telomerase, especially the rate-limiting determinant of telomerase activity. Accumulating evidence has suggested that TERT could modulate the expression of numerous genes including interleukin 6 (IL-6), an important cytokine for the development of lung cancer. It has been reported that TERT polymorphism rs2736100T/G is associated with increased susceptibility to non-small cell lung cancer (NSCLC). However, the mechanism remains unclear. In the current study, we investigated the association between rs2736100T/G and NSCLC in 1,552 NSCLC and 1,602 healthy controls. Data revealed that the prevalence of TG and GG genotypes were significantly elevated in patients than in controls (odds ratio (OR) = 1.18; 95% confidence interval (CI), 1.01-1.39; p = 0.040 and OR = 1.46; 95% CI, 1.19-1.78; p < 0.001, respectively). The association was more prominent in patients with lung adenocarcinoma than those with squamous cell carcinoma (p = 0.039). When analyzing the function of the polymorphism, we observed a significantly augmented level of IL-6 in subjects with GG genotype than those with GT and TT genotypes. Interestingly, the upregulation of IL-6 by GG genotype was 2.3-fold higher in lung adenocarcinoma compared to squamous cell carcinoma. These results suggest that the rs2736100T/G polymorphism modulates IL-6 expression and may play a unique role in lung adenocarcinoma.