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Krüppel-like factor 4 (KLF4) is an evolutionarily conserved zinc finger-containing transcription factor. In the present study, peripheral blood mononuclear cells and phorbol 12-myristate 13-acetate-differentiated THP-1 cells were treated with oxidized low-density lipoproteins and high-density lipoproteins to determine the expression of KLF4 and scavenger receptor class B type I (SR-BI). A full-length cDNA of KLF4 or short interference RNA against KLF4 was transfected into THP-1 cells, and the subsequent expressions of SR-BI were analysed by real-time PCR and western blot. The binding and transcriptional activities of KLF4 to the SR-BI promoter were detected by electrophoretic mobility shift assay, chromatin immunoprecipitation assay and luciferase reporter assay. The results showed that induction of KLF4 by high-density lipoproteins could promote the expression of SR-BI, resulting from the binding to putative KLF4 binding element on the promoter of SR-BI. All results indicate a potential function of KLF4 in the pathogenesis of atherosclerosis through the regulation effect on atherosclerotic-related genes.