Long intergenic noncoding RNAs (lincRNAs) have critical regulatory roles in cancer biology; however, the contributions of lincRNAs to esophageal squamous cell carcinoma (ESCC) have been infrequently explored. The aim of this study was to explore the contribution of lincRNAs, located at ESCC susceptibility loci identified by genome-wide association studies, to the risk and prognosis of ESCC. The associations between lincRNAs and the risk and prognosis of ESCC were analyzed in 358 diagnosed patients from eastern China, and the findings were validated in 326 additional patients from southern China. Functional relevance of lincRNAs was further examined by biochemical assays. We found that lincRNA-uc002yug.2 was commonly overexpressed in ESCC compared with paired peritumoral tissue in eastern and southern Chinese populations. The expression levels of lincRNA-uc002yug.2 in ESCC might be a prognostic factor for survival. Moreover, lincRNA-uc002yug.2 promoted a combination of RUNX1 and alternative splicing (AS) factors in the nucleus to produce more RUNX1a, the short isoform and inhibitor of RUNX1, and reduce CEBPα (CCAAT/enhancer-binding protein-α) gene expression, thereby promoting ESCC progression. These results indicated that lincRNA-uc002yug.2 might involve in AS of RUNX1/AML1 and serve as a predictor for esophageal cancer and prognosis.