Objective Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in industrialized countries. Recent studies have highlighted the association between peroxisomal dysfunction and hepatic steatosis. Peroxisomes are intracellular organelles that contribute to several crucial metabolic processes such as β-oxidation of fatty acids and biosynthesis of plasmalogens. Plasmalogens are key structural components of the cell membrane, and protect cells from ROS-induced damage. Methods Seven-week-old C57BL/6J mice were divided into 3 groups (n = 7 each), and given normal chow or methionine choline-deficient diet (MCDD) with or without fluvastatin (15 mg/kg/d) for 6 weeks. We measured mitochondrial and peroxisomal fatty acid oxidation (FAO) and plasmalogen levels in the liver. We also examined the expression of genes involved in lipid metabolism. Results Fluvastatin treatment prevented the development of nonalcoholic steatohepatitis (NASH) in MCDD-fed mice. Feeding MCDD decreased and fluvastatin treatment increased mitochondrial and peroxisomal FAO, and peroxisomal proliferator-activated receptor (PPAR)-α expression, respectively. MCDD decreased hepatic plasmalogen levels and the expression of enzymes responsible for plasmalogen synthesis. This was recovered by fluvastatin administration. Fluvastatin treatment also increased the expression of Δ-5/6 desaturases. siRNA-mediated inhibitions of Δ-6 desaturase or plasmalogen synthesis enzymes increased cell apoptosis and expression of inflammation markers in cultured hepatocytes. Conclusion We suggest a new possibility that improvement of peroxisomal FAO and plasmalogen synthesis by statins might contribute to the prevention of NASH in MCDD-fed mice.