Krüppel-like transcription factors (KLFs) play a key role in both vascular development and pathophysiological processes, but little is known about the relationship between KLFs and oxidized low-density lipoprotein (ox-LDL). We investigated the effects of ox-LDL on KLF expression. Furthermore, since atorvastatin is commonly used to treat high cholesterol, we also examined the role of this drug in the regulation of KLF expression. The human umbilical vein endothelial cell line EA.hy926 was treated with atorvastatin and ox-LDL alone or in combination, and KLF expression was examined by DNA microarray, semi-quantitative real-time PCR, western blot and immunofluorescence analyses. Atorvastatin upregulated KLF expression in EA.hy926 cells in both the quiescent and ox-LDL-induced inflammatory states, suggesting that KLFs were novel participants in the vascular endothelial dysfunction response to ox-LDL. Our study demonstrated that atorvastatin increased both the mRNA and protein levels of KLF in quiescent EA.hy926 cells. Moreover, atorvastatin counteracted the ox-LDL-induced downregulation of KLF expression.