Abstract: In order to investigate the antioxidant effect of the extract of Euphorbia helioscopia in vitro and its effect on lipid accumulation in HepG2 cells induced by oleic acid. In this study, 25%, 50%, 75% methanol and ethanol were used to extract the powder by immersion method. The antioxidant activities of the different extracts were assessed, and the levels of total phenols and total flavonoids were measured. To establish a model of lipid accumulation in HepG2 cells, the cells were treated with 50% ethanol extract (at concentrations of 20, 40, and 60 μg/mL) for 24 h to observe the formation of lipid droplets. The triglyceride (TG) content, total glutathione (GSH), superoxide dismutase (SOD) activity, and total antioxidant capacity (T-AOC) in the cells were determined. The findings demonstrated that all extracts exhibited concentration-dependent antioxidant activity. Among them, the 50% ethanol extract exhibited the most potent antioxidant effect in a certain concentration range (P<0.05), with higher levels of total phenols (8.813%±1.344%) and total flavonoids (17.938%±0.819%) . Compared with the model group, the 50% ethanol extract displayed a concentration-dependent ability to decrease lipid droplets and TG values in HepG2 cells, while increasing the levels of GSH, T-AOC, and SOD activity. Therefore, the 50% ethanol extract showed potential in inhibiting oleic acid-induced fat accumulation in HepG2 cells and enhancing the endogenous antioxidant capacity of the cells.