Aim To investigate whether there is a difference between HDLPCHD and HDL_health against human umbilical vein endothelial cells apoptosis in patients with premature coronary heart disease (PCHD) and the possible mechanism. Methods Blood samples of PCHD patients and healthy subjects were collected, and HDL was isolated from the blood samples. Human umbilical vein endothelial cells were treated for 24 hours with different concentrations of oxidized low density lipoprotein (ox-LDL), cell viability was detected by MTT, to identify the appropriate concentration of ox-LDL induced human umbilical vein endothelial cells cell apoptosis. Human umbilical vein endothelial cells were pretreated with different hours and different concentration of HDL_health, then treated with the appropriate concentration of ox-LDL for 24 hours, cell viability was detected by MTT, to identify the optimal concentration and time of HDL_health pretreated human umbilical vein endothelial cells. Human umbilical vein endothelial cells were pretreated with the optimal hours and the optimal concentration of HDL_health and HDLPCHD, then treated with the appropriate concentration of ox-LDL for 24 hours, cell viability was detected by MTT. Annexin V-FITC/PI apoptosis detection kit was used for flow cytometry staining, Western blot was used to detect Caspase 3 and Caspase 9 protein expression, kit was used to detect the activity of reactive oxygen species (ROS), sub-fraction (HDL₁-HDL₁₀) distribution of HDL_health and HDLPCHD were analyzed by Lipoprint System. Results Human umbilical vein endothelial cell survival rate was 60.34% after treatmented with 100 mg/L ox-LDL for 24 hours, which was significantly lower than that in the blank treatment group (P＜0.05). Human umbilical vein endothelial cell survival rate was 82.01% after pretreated with 200 mg/L HDL_health for 18 hours, which could significantly reduce the damage of ox-LDL to cells. 200 mg/L HDL_health could significantly inhibit apoptosis of human umbilical vein endothelial cells, the expression of Caspase 3 and Caspase 9 and the production of ROS , which were induced by 100 mg/L ox-LDL. Human umbilical vein endothelial cell survival rate was 65.5% after pretreated with 200 mg/L HDLPCHD for 18 hours, and its effect was weaker than that of HDL_health. 200 mg/L HDLPCHD could inhibit apoptosis of human umbilical vein endothelial cells, the expression of Caspase 3 and Caspase 9 and the production of ROS induced by 100 mg/L ox-LDL, but the effect was weaker than that of HDL_health. The content of large particle (HDL₁-HDL₃) in HDLPCHD subgroup was lower than that in HDL_health (28.5%±5.7% vs. 46.8%±15.2%), while the content of small particle (HDL₈-HDL₁₀) was higher than that of HDL_health (21.4%±7.8% vs. 10.9%±5.4%). Conclusion Comparison to the HDL_health, perhaps due to the large particle of HDLPCHD sub-fraction content (HDL₁-HDL₃) was lower than that of HDL_health, while the small particle was higher than that of HDL_health (HDL₈-HDL₁₀), resulting in antioxidant function weakened, inhibiting the apoptosis of endothelial cells induced by ox-LDL were decreased, thereby weakening or losing the role of anti-atherosclerosis.