In conclusion, our study confirmed that Rnase6 promoter hypomethylation accelerated the proliferation, migration and inflammatory infiltration of injured vascular smooth muscle cells and aggravated atherosclerosis in mice by activating the PI3K/AKT/mTOR signaling pathway, which provided more ideas for finding potential therapeutic targets for atherosclerosis. This evidence concerns the gene RNASE6 and atherosclerosis.