Polymorphisms of the NR3C1 (glucocorticoid receptor) gene have been reported to be associated with altered glucocorticoids sensitivity and changes in body composition and metabolic parameters. This study explored the relationship between single nucleotide polymorphisms (SNPs) of the NR3C1 gene and metabolic syndrome (MetS) in a Chinese population. Fourteen tag-SNPs and five functionally important SNPs in the NR3C1 gene were genotyped in MetS patients (n = 431) and normal controls (n = 461) using the high-throughput Sequenom genotyping platform. Genotype, allelic and haplotype associations were examined using logistic regression and Haploview. There are four SNPs significantly associated with MetS. The T allele of rs2963156 was associated with an increased risk effect for MetS (adjusted OR = 1.66, 95 % CI 1.25-2.22, P = 0.001). By contrast, rs10052957 A allele carriers were significantly associated with a decreased risk of MetS (adjusted OR = 0.58, 95 % CI 0.42-0.80, P = 0.001). Rs41423247 GG genotype (adjusted OR = 2.01, 95 % CI 1.25-3.22, P = 0.004), and rs7701443 AA genotype (adjusted OR = 1.88, 95 % CI 1.24-2.83, P = 0.003) were significantly associated with an increased risk of MetS. Haplotype CGGA is risk conferring (adjusted OR = 1.53, 95 % CI 1.06-2.20, P = 0.023), whereas haplotype CCAG was protective (adjusted OR = 0.30, 95 % CI 0.20-0.47, P < 0.001). Polymorphism of NR3C1 gene is associated with MetS and may contribute to the susceptibility of MetS.