Aim To investigate whether proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates monocyte-endothelial cell adhesion through Toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB)/cyclooxygenase-2 (COX-2) pathway in human umbilical vein endothelial cells (HUVECs). Methods HUVECs were incubated with oxidized low density lipoprotein (ox-LDL), real-time PCR and Western blot assay for detection of PCSK9, TLR4, NF-κB, COX-2 mRNA and protein expression. After treatment with ox-LDL, recombinant PCSK9 protein was incubated or PCSK9 siRNA was transfected into HUVECs. Then the expression of TLR4, NF-κB p65, COX-2 mRNA and protein was detected. After treatment with ox-LDL, human recombinant PCSK9 protein was incubated with TLR4 inhibitor TAK-242 or NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) to detect mRNA and protein expression of NF-κB p65 and COX-2. After COX-2 inhibitor (NS398) and human recombinant PCSK9 protein were treated successively, THP-1 monocytes were added and monocyte-endothelial cell adhesion was detected. Results ox-LDL up-regulates the mRNA and protein expression of PCSK9, TLR4, NF-κB and COX-2 in HUVECs (all P＜0.05). Human recombinant PCSK9 protein up-regulated TLR4, NF-κB, COX-2 mRNA and protein expression on ox-LDL basis (all P＜0.05). PCSK9 siRNA transfection down-regulated the up-regulation of TLR4, NF-κB, COX-2 mRNA and protein expression by ox-LDL (all P＜0.05). TAK-242 inhibits the up-regulation of TLR4 and NF-κB mRNA and protein expression by human recombinant PCSK9 protein (all P＜0.05). PDTC inhibits the up-regulation of NF-κB and COX-2 mRNA and protein expression by human recombinant PCSK9 protein (all P＜0.05). NS398 inhibits monocyte-endothelial cell adhesion induced by human recombinant PCSK9 protein (all P＜0.05). Conclusion PCSK9 regulates monocyte-endothelial cell adhesion via TLR4/NF- κ B/COX-2 pathway.