Abstract: OBJECTIVE To explore the effect and mechanism of Daidai flavonoid extracts and its key effect components on the regulation of lipid metabolism in steatosis cells and to identify the key effect components. METHODS HepG2 cell steatosis model was established by oleic acid induction. Fenofibrate was used as a positive control. The oil red O staining method, triglycerides(TG), and total cholesterol(TC) were used as evaluating indicators to investigate the effects of Daidai flavonoid extracts, naringin(key effect component), neohesperidin(key effect component), other related components(flavonoid extract excluded naringin and neohesperidin), and extracts excluded other related components(6:7 of naringin-neohesperidin) on the lipid accumulation in HepG2 cell steatosis model. Based on AMPK/SREBP-1c and PPARα signaling pathways, qRT-PCR and Western blotting were used to detect the expression of related genes and proteins in rat liver. RESULTS After preventive administration, compared with the model group, the cell lipid accumulation, TG and TC levels were significantly improved(P<0.01 or P<0.05) in the groups of Daidai flavonoid extracts, naringin, neohesperidin and extracts excluded other related components. Daidai flavonoid extracts, naringin and neohesperidin significantly increased the expression levels of ATP-activated protein kinase(AMPK) mRNA and phosphorylated protein(P<0.01 or P<0.05); inhibited and reduced the mRNA and protein expression levels of sterol regulatory element binding protein(SREBP-1c), fatty acid synthase(FAS) and acetyl coenzyme carboxylase(ACC)(P<0.01 or P<0.05); increased the mRNA and protein expression levels of peroxidase proliferator-activated receptor(PPARα) and carnitine palmitoyltransferase-1(CPT-l)(P<0.01 or P<0.05). There was no significant difference in other related component group. CONCLUSION The Daidai flavonoid extracts and the key effect components naringin and neohesperidin can effectively improve the lipid accumulation of steatosis model cells. The mechanism is to activate AMPK to promote its phosphorylation expression, thereby inhibiting lipid synthesis. At the same time, it promotes the oxidation and decomposition of fatty acids, thereby reducing fat deposition and regulating lipid metabolism.