Considering the involvement of the 5p15.33 TERT-CLPTM1L locus in ESCC is still largely unclear, we examined the associations between 15 haplotype-tagging SNPs (htSNP) across the TERT-CLPTM1L locus and ESCC risk in three large independent hospital-based case-control studies. This evidence concerns the gene TERT and esophageal squamous cell carcinoma.