Aim To investigate the role of microRNA-34a(miR-34a)in human aortic endothelial cells(HAEC)apoptosis during atherosclerosis(As)and the underlying mechanism. Methods HAEC were treated with oxidized low-density lipoprotein(ox-LDL). The expression level of miR-34a was detected using qRT-PCR. Apoptosis was determined via flow cytometry(FCM)and Caspase-3 activity assay. Prediction of the binding between miR-34a and 3′UTR of Sirt1 mRNA was performed by bioinformatics analysis and confirmed by a dual luciferase reporter assay. Results miR-34a expression was substantially up-regulated during the ox-LDL-elicited apoptosis in HAEC. Forced expression of miR-34a promoted HAEC apoptosis whereas inhibition of miR-34a could partly alleviate apoptotic cell death induced by ox-LDL. Further analysis identified Sirt1 as a direct target of miR-34a, and Sirt1 knockdown abolished the anti-apoptotic effect of miR-34a inhibitor. Moreover, overexpression of miR-34a enhanced the expression of acetylated of FoxO1, downregulation of miR-34a repressed the protein expression of acetylated-FoxO1. Conclusion Down-regulation of miR-34a inhibited HAEC apoptosis by regulating the expression of Sirt1/FoxO1 signaling pathway.