Esophageal carcinoma (EC) is a common malignancy worldwide. Previous studies indicated that gastrointestinal gland cancer and EC share some susceptibility loci. Our aim was to identify new single nucleotide polymorphisms (SNPs) associated with EC by investigating whether known gastrointestinal cancers susceptibility loci are found in EC patients. A Chinese Han population case–control study was conducted to assess SNP associations with EC risk. Twenty-six SNPs were selected from gastrointestinal cancer susceptibility loci, and 360 EC patients and 310 controls were genotyped for these SNPs using Sequenom MassARRAY technology. The association of SNP frequencies with EC was analyzed by chi-square tests, and genetic model analysis. After Hardy–Weinberg equilibrium (HWE) p value screening, we excluded two SNPs. Based on chi-square tests, the minor alleles of rs13294589 (p = 0.046) and rs4924935 (p = 0.046) were correlated with reduced EC risk and rs4269383 (p = 0.010) and rs10953615 (p = 0.036) were correlated with increased EC risk. In the genetic model analyses, we found that the minor alleles “T” of rs401681, “A” of rs10088262, and “C” of rs4924935 may reduce the risk of EC. rs401681 has previously been reported to be associated with EC. To the best of our knowledge, we are the first to report an association of the other five SNPs with EC. Our findings provide evidence for the genetic variants associated with susceptibility to EC in the Chinese Han population, which might be used as potential molecular markers for detecting susceptibility to EC in Chinese Han people.