Insulin-like growth factor binding protein-3 (IGFBP-3) exerts anti-proliferative or pro-apoptotic effects through IGF-dependent as well as IGF-independent mechanisms in vitro. The purpose of this study was to examine the association between genetic variants in IGFBP-3 (rs2270628) and the risk of esophageal squamous cell carcinoma (ESCC) in a Chinese Han population. Five hundred ESCC cases and 500 cancer-free controls of the Chinese Han population were involved in this study. The IGFBP-3 single-nucleotide polymorphism (SNP) rs2270628 was genotyped and the estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for its association with the risk of ESCC were determined using unconditional logistic regression analysis. Compared with the rs2270628 CC genotype, TT genotype was associated with a significantly increased ESCC risk with OR (95%CI) of 2.07 (1.05-4.09), but CT genotype was not (OR = 1.25, 95%CI =0.94-1.66). IGFBP-3 SNP rs2270628 may contribute to the risk of ESCC in the Chinese Han population.