Abstract: According to the synthetic method of organic selenium compounds, this paper was based on Lycium barbarum polysaccharide and sodium selenite. The technological conditions of selenium polysaccharide were optimized by the response surface method. The optimal conditions of selenium were screened by single factor and best value screening and response surface analysis using atomic fluorescence and in vitro chemical reaction system. According to the addition of LBP as 1 g, adding 0.62 g Na₂SeO₃, with 1% HNO₃ fully dissolved, then adding BaCl₂ 1 g, with oil bath 74℃ reaction 9 h. Under the optimized extraction conditions, the selenium content of polysaccharide from Lycium barbarum was 648.65 μg/g. The activity results showed that Lycium barbarum polysaccharides and selenium polysaccharide had a certain inhibition effect on HepG2 cells, all the inhibitory effect of selenium polysaccharide of Lycium barbarum polysaccharide was superior, and the inhibitory effect of Se-LBP₄ was the highest content of selenium on tumor cells of HepG2 was best, the inhibition rate was 38.15%. There was a positive correlation between the inhibition of HepG2 proliferation and the content of selenium in Lycium barbarum selenium polysaccharide, which was expected to be further developed as the raw material for food, health food and medicine.