The development of esophageal squamous cell carcinoma (ESCC) is a multifactorial process, and associations between genetic variants (GVs) and ESCC have been identified in genome-wide association studies (GWAS). The aim of this study was to evaluate the effects of single nucleotide polymorphisms (SNPs) of long intergenic non-coding RNAs (lincRNAs) on ESCC susceptibility in Chinese populations. We scoured exons of lincRNAs located in ESCC susceptibility loci for all probable functional SNPs. These 52 SNPs were opted for and genotyped in 1493 ESCC patients and 1553 cancer-free controls from eastern and southern Chinese populations, and their associations with the risk for ESCC were estimated using logistic regression. Functional relevance was further examined by biochemical assays. Significant differences were found between patients and controls in the genotype frequencies for the rs11752942A>G site in the lincRNA-uc003opf.1 exon. Compared to the rs11752942AA genotype, AG and GG genotypes had a significantly reduced risk of ESCC (adjusted odds ratios [OR]=0.73; 95% confidence interval [CI]=0.63-0.84). Biochemical analysis demonstrated that, when compared with the A allele, the rs11752942G allele can markedly attenuate the level of lincRNA-uc003opf.1 both in vivo and in vitro by binding microRNA-149*, thereby affecting cell proliferation and tumor growth. These findings indicate that functional polymorphism rs11752942A>G in lincRNA-uc003opf.1 exon might be a genetic modifier for the development of ESCC.