Atherosclerosis is a chronic inflammatory disease caused by various pathogenic factors. Lipid metabolism disorders have a fundamental role in the pathogenesis of atherosclerosis. The liver is the largest metabolic organ in humans and has a key role in lipid metabolism by influencing fat production, fat decomposition, and the intake and secretion of serum lipoproteins. By targeting hepatic lipid metabolism, research and development studies have focused on novel lipid-lowering strategies. Here, we review novel approaches to target the regulation of liver lipid metabolism for the treatment of atherosclerosis, including new biomarkers, therapeutic targets, traditional Chinese medicine, and natural dietary supplements.