In this study,response surface methodology (RSM) and MTT colorimetry were used to study the sulfation process of dandelion root polysaccharide and the protective effects of dandelion root polysaccharide and its sulfation on oxidative damage of HepaRG cells induced by hydrogen peroxide (H₂O₂).The results showed that the optimum conditions for sulfation of dandelion root polysaccharides were as follows: reaction temperature was 83 ℃,ratio of pyridine to chlorosulfonic acid was 8,reaction time was 3 h.Moreover,dandelion root polysaccharide and its sulfates had protective effects on H₂O₂ induced oxidative damage of HepaRG cells,and the activity of sulfated dandelion root polysaccharide was better than that of dandelion root polysaccharide.