Aim To investigate the role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in the apoptosis of human umbilical vein endothelial cells induced by nitrated low density lipoprotein (N-LDL) and its molecular mechanism. Methods Differential expression analysis was performed using publicly available transcriptome datasets to assess the correlation between N-LDL and PCSK9 expression in relevant diseases. Human umbilical vein endothelial cells were treated with N-LDL to induce apoptosis, which was detected by Hoechst33342/propidium iodide (PI) staining. Expression of apoptosis-related molecules was assessed by Western blot. Reactive oxygen species (ROS) production and mitochondrial membrane potential were measured using dihydroethidium (DHE) and JC-1 probes, respectively. Lipid accumulation in human umbilical vein endothelial cells was evaluated by oil red O staining. PCSK9 knockdown was achieved using siRNA. Results Following N-LDL treatment of human umbilical vein endothelial cells, CCK-8 assay results demonstrated a significant decrease in cell viability compared with both the control and LDL groups (P＜0.01). Western blot analysis showed markedly increased expression of the pro-apoptotic proteins Caspase-9, Caspase-3 and Bax, accompanied by a significant reduction in the anti-apoptotic protein Bcl-2 (P＜0.01). Hoechst33342/PI double staining revealed an increased number of positive cells, indicating the occurrence of apoptosis. N-LDL upregulated the protein expression of the key cholesterol metabolism transcription factor sterol regulatory element-binding protein 2 (SREBP2) and its downstream target protein PCSK9 in a concentration-dependent manner (P＜0.05), with a consistent trend of both. Oil red O staining demonstrated that N-LDL treatment promoted intracellular lipid accumulation. Moreover, flow cytometry and fluorescence analyses showed that N-LDL increased intracellular reactive oxygen species (ROS) production and significantly reduced mitochondrial membrane potential (P＜0.05), indicating mitochondrial dysfunction. Notably, silencing PCSK9 significantly reversed these N-LDL-induced mitochondrial dysfunction and apoptotic alterations in human umbilical vein endothelial cells, as evidenced by reduced ROS production, restoration of mitochondrial membrane potential, decreased expression of Caspase-9 , Caspase-3 and Bax, upregulated Bcl-2 expression, and a decreased number of PI-positive cells (P＜0.05). Conclusion N-LDL upregulates SREBP2 expression, promotes the expression of PCSK9, thereby activating the mitochondrial apoptosis pathway, and ultmately inducing apoptosis in human umbilical vein endothelial cells.