In this hospital-based case-control study of ESCC, we investigated the association of OPG rs3102735 C>T, OPG rs2073618 G>C, RANK rs1805034 T>C, RANKL rs9533156 T>C and RANKL rs2277438 A>G polymorphisms with risk of ESCC in a Chinese population. This evidence concerns the gene TNFRSF11B and esophageal squamous cell carcinoma.