Abstract: The polysaccharides of Schisandra chinensis were extracted by ultrasonic-assisted cellulase enzymolysis from the dried fruit of S. chinensis as raw material, and the extraction process and anti-oxidative stress activity of S. chinensis polysaccharides were studied. Using polysaccharide yield as index, single factor experiment and Box-Behnken response surface test were used to investigate the effects of enzyme concentration, ultrasonic power, extraction time and solid-liquid ratio on polysaccharide yield of S. chinensis, and the ultrasonic-assisted enzymatic extraction process was optimized. A lipopolysaccharide（LPS） induced oxidative stress damage model of HepG2 cells was established, and the levels of malondialdehyde（MDA）, superoxide dismutase（SOD） and reactive oxygen species（ROS） were used as indicators, and the anti-oxidative stress ability of S. chinensis polysaccharides was investigated. The results showed that the optimal extraction conditions as followed: the enzyme concentration was 1 420 U·g^-1, the ultrasonic power was 500 W, the extraction time was 46 min, the solid-liquid ratio was 1 g:32 mL. Under these conditions, the yield of polysaccharides was 22.25%. Moreover, the extracted S. chinensis polysaccharides might improve the SOD level in the LPS-induced HepG2 cells, but reduce the MDA accumulation and ROS fluorescence intensity in the cells, and effectively relieve the LPS-induced oxidative stress in HepG2 cells. The extraction conditions of polysaccharides from S. chinensis were optimized, and it was found that the extracted polysaccharides had good antioxidant stress ability.