Objective To explore the association between variant rs4299376 of ABCG5/ABCG8 gene with the risk of coronary heart disease (CHD) in Han Chinese and the association of related lipid levels with CHD. Methods We collected blood samples from 290 CHD cases, 198 non-CHD controls and 331 healthy controls. The genomic DNA was acquired by the nucleic acid extraction automatic analyzer and the rs4299376 genotypes were analyzed by the Mass-ARRAY iPLEX^R platform. Results There were no significant differences in distribution of variant rs4299376 of ABCG5/ABCG8 gene among Han Chinese with CHD, non-CHD controls and healthy controls. There was no association between lipid levels and CHD in either total or male groups. While in female group, the triglyceride (TG) and total cholesterol (TC) were higher in CHD patients than in non-CHD controls (TG: 2.23±1.05 vs 1.84±1.03, P=0.01; TC: 4.79±1.17 vs 4.36±1.03, P=0.01). It was also found that, for those 60 years old and above, the CHD cases had a significantly lower high density lipoprotein (HDL) level compared with non-CHD group (1.09±0.23 vs 1.16±0.25, P=0.03). Conclusion There is no noticeable association between ABCG5/ABCG8 rs4299376 polymorphism and the risk of CHD in Han Chinese. Female CHD patients have higher levels of TG and TC, and when over 60 year old, CHD patients have a lower HDL level than non-CHD controls.