Aim To explore whether the hxeroderma pigmentosum D(XPD) could mediate the apoptosis of human umbilical vein endothelial cells (HUVEC) promoted by oxidized low density lipoprotein (ox-LDL). Methods The model of apoptosis of HUVEC was established by ox-LDL. XPD-siRNA was transfected into HUVEC with liposome,followed by treatment with ox-LDL. This experiment was divided into six groups:blank control group; negative control siRNA group; XPD-siRNA group; ox-LDL group; ox-LDL+negative control siRNA group; ox-LDL+XPD-siRNA group. Cell vitality was detected by MTT; Cell apoptosis rate and cell cycle were assessed with flow cytometry; The expressions of the XPD, Bax and Bcl-2 were detected by RT-PCR and Western blot. Results The optimal concentration of ox-LDL to establish the model of apoptosis of HUVEC was 100 mg/L. Compared with negative control siRNA group, the cell apoptosis rate of XPD-siRNA group was significantly decreased (P<0.05), the survival rate was significantly increased (P<0.01), the cell number in G0/G1 phase decreased (P<0.05), while increased in S phase (P<0.05), the expressions of XPD and Bax were declined (all P<0.05), while the expression of Bcl-2 was elevated (P<0.05); Compared with blank control group, the cell apoptosis rate of ox-LDL group increased significantly (P<0.01), the survival rate was decreased (P<0.05), the cell number in G0/G1 phase increased (P<0.05),while decreased significantly in S phase (P<0.01), the expressions of XPD and Bax were elevated (all P<0.05),while the expression of Bcl-2 was declined (P<0.05). Compared with ox-LDL+negative control siRNA group,the cell apoptosis rate of ox-LDL+XPD-siRNA group was reduced (P<0.05),the survival rate was increased(P<0.01), the cell number in G0/G1 phase decreased (P<0.05),while increased in S phase (P<0.05), the expressions of XPD and Bax were declined (all P<0.05), while the expression of Bcl-2 was elevated (P<0.05). Conclusion XPD can mediate the effect of ox-LDL on promoting the apoptosis of HUVEC.