Background: Altered expression of six-transmembrane epithelial antigen of prostate 4 (STEAP4) is linked to obesity, insulin insensitivity, metabolic homeostasis, and inflammation. This study assessed STEAP4 single nucleotide polymorphisms (SNPs) for association with a risk in developing metabolic syndrome in a Han Chinese population. Methods: A total of 3375 Han Chinese subjects were included in this case-control study with 1583 metabolic syndrome (MetS) patients and 1792 healthy controls. Four SNPs (rs1981529, rs2040657, rs10263111, rs12386756) were genotyped using polymerase chain reaction and MALDI-TOF-MS. The associations between the STAMP4 SNPs and MetS were then analyzed statistically. Results: There was no statistical difference in allele frequency of these four SNPs between the case and control populations. The genotype of rs12386756 was shown to be significantly associated with MetS ( p = 0.035). Compared with the AA/GG genotypes, the GA genotype of rs12386756 significantly decreased the risk of developing MetS (OR = 0.77; 95% CI, 0.63-0.94; p = 0.0098). There was also no haplotype that could be associated with the risk of developing MetS. Furthermore, the SNP rs1981529 of STEAP4 was associated with body-mass index, waist circumference, and systolic blood pressure, while SNP rs10263111 was associated with waist circumference and fasting glucose levels. SNP rs12386756 was associated with waist and hip circumferences. Conclusion: Some SNPs of the STEAP4 gene altered the risk of developing a metabolic syndrome in the Han Chinese population. Further studies must be conducted to understand the role of the STEAP4 gene in the pathogenesis of metabolic syndrome.