Aim To investigate the effect of oxidized low density lipoprotein （ox-LDL） on the expression of plant homeodomain finger-2 （PHF-2） and explore the potential effect of epigenetic regulation on ox-LDL-induced inflammatory response in macrophages. Methods THP-1 macrophages were exposed to ox-LDL with different levels （0, 50, 100, 150 mg/L） for 4 h. Enzyme linked immunosorbent assay was used to determine levels of tumor necrosis factor-α （TNF-α） and macrophage inflammatory protein-1β （MIP-1β）. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to determine mRNA and protein levels of PHF-2. Coimmunoprecipitation was used to determine the interaction of PHF-2 and p65 nuclear factor-kappa B （p65 NF-κB）. Results ox-LDL from 100 mg/L to 150 mg/L increased the levels of TNF-α and MIP-1β. PHF-2 mRNA and protein were induced by ox-LDL in a concentration-dependent manner in THP-1 macrophages. Ox-LDL promoted the interaction of PHF-2 and p65 NF-κB. Conclusion PHF-2 may play a crucial role in the NF-κB activation and proinflammatroy cytokines expression in THP-1 macrophages.