Abstract Background Nuclear receptor coactivator-3 (NCOA3) is involved in various physiological processes. Emerging evidence from previous studies using animal models suggests that the NCOA3 gene ( NCOA3 ) plays a critical role in lipid metabolism as well as adipogenesis and obesity. The present study aims to investigate the association between NCOA3 SNPs and dyslipidemia in the Chinese Han population. Methods Five hundred and twenty-nine (529) Chinese Han subjects were recruited. Four tag SNPs (rs2425955G > T, rs6066394T > C, rs10485463C > G, and rs6094753G > A) in NCOA3 , selected from the HapMap website, were genotyped using MALDI-TOF mass spectrometry. Data analysis was performed using SPSS 16.0, SNPStats and haploview 4.2. Results Four SNPs (rs2425955, rs6066394, rs10485463, and rs6094753) were associated with triglyceride levels. Except for SNP rs10485463, genotype distributions and allele frequencies of the other three NCOA3 SNPs (rs2425955, rs6066394, and rs6094753) were significantly different between hypertriglyceridemia subjects and normal group. Significant differences were also observed in allele frequencies and genotype distributions of SNP rs10485463 between low-HDL cholesterolemia subjects and normal group. Carriers of rs2425955 T allele had a lower risk of hypertriglyceridemia compared to GG genotype. Similar results were observed from rs6094753. Subjects with rs6066394 CT genotype had a lower risk of hypertriglyceridemia than those with the TT genotype; however, CC and TT genotypes showed no significant difference in the risk of hypertriglyceridemia. Similar results were found in the association between rs6066394 and hypercholesterolemia. The variant alleles of rs2425955, rs6066394 and rs6094753 were associated with a lower risk of hypertriglyceridemia compared with the wild-type alleles. The G allele of rs10485463 was associated with an increased risk of low-HDL cholesterolemia. In the log-additive model the association between rs2425955 and hypertriglyceridemia remained significant after Bonferroni correction, and genotypes with variant alleles were associated with a lower risk of hypertriglyceridemia. Conclusions In summary, this study demonstrated that variation in NCOA3 might influence the risk of dyslipidemia and serum lipid levels in Chinese Han population.