Background: There was no previous study to report the association between single nucleotide polymorphisms (SNPs) of hyperplasia suppressor gene (HSG) and serum lipid traits in any population. The purpose of the present study was to firstly investigate their association. Methods and Results: A total of 674 hypertensive participants were included in the current study. We genotyped three HSG SNPs by TaqMan PCR method. Overall, subjects carrying rare type genotypes of rs2295281 and rs3753579 were obviously associated with higher triglyceride (TG). For rs1810563, subjects carrying AA genotype were associated with elevated TG. No association was found for the rest serum lipids. Subsequently participants were divided into 2 groups according to sex and body mass index. In women subgroup, low-density lipoprotein (LDL) was significantly high in C allele carriers of rs2295281 compared with TT genotype. In men, total cholesterol (TC), TG and LDL showed significant correlation with rs2295281, rs3753579 and rs1810563, respectively. No association was observed for the obese subgroup. For the case-control study, we found significant association between rs2295281 and the increased risk of hypertriglyceridemia in the recessive model (P=0.016, OR=1.85, 95% CI (1.12-3.05)) and homozygote model (P=0.035, OR=1.78, 95% CI (1.04-3.04)). Conclusion: The genetic variants of HSG may be associated with serum lipid traits (particularly TG) in Chinese patients with hypertension.