To study the effects of 4-hydroxy-2-nonenal (HNE) on cultured human aortic endothelial cells and myocardial cells so as to explore the mechanism of the pathogenesis of atherosclerosis. In situ cell death technique, quantitative DNA damage detection and immunohistochemistry were used to identify the cell apoptosis and DNA damage in cultured human aortic endothelial cells and myocardial cells. Tail moment was 32.80±1.12, 44.30±0.99 and 74.6±0.97 when HAOEC were treated with 5 μM, 10μM and 15 μM of HNE for 10 hours, which were of statistical significance when compared with the normal group (6.0±0.67, P0.05). When human aortic endothelial cells (HAOEC) were treated with 5 μM, 10μM and 15 μM of HNE for 10 hours, the percent of nonviable cells were 5.70±0.55, 25.96±2.02 and 50.80±3.40 (P0.05). When cultured human myocardial cells were treated with 5 μM of HNE for 10 hours, TUNEL staining showed a greater number of apoptotic cells in HNE-treated human myocardial cells. No TUNEL-positive cells were observed in untreated group.