Aim To study the effects of 4-hydroxy-2-nonenal (HNE) on cultured human aortic endothelial cells so as to explore the mechanism of the pathogenesis of atherosclerosis. Methods In single cell gel electrophoresis, quantitative DNA damage detection was used to identify the DNA damage at different concentrations in cultured human aortic endothelial cells. Results Tail moment was 32.8±1.1, 44.3±1.0 and 74.6±1.0 when human aortic endothelial cells were treated with 5 μmol/L, 10 μmol/L and 15 μmol/L of HNE for 10 hours, which were of statistical significance when compared with the normal group (6.0±0.7, p<0.001 respectively), but when human aortic endothelial cells was treated with 1 μmol/L of HNE, the tail moment was 11.3±0.9, which was of no statistical difference compared with the untreated group(p>0.05). Conclusion HNE induces DNA damage of cultured aortic endothelial cells. The DNA damage levels are proportional to the HNE concentrations.