Abstract: Objective: To investigate the factors affecting the hygroscopicity of Polygonatum odoratum polysaccharide and to develop moisture-resistant intermediate tablets. Methods: The contents of polysaccharide, protein and fructose in Polygonatum odoratum polysaccharide powder and the indicators characterizing the properties of Polygonatum odoratum polysaccharide powder, such as median diameter D50, distribution span, specific surface area, angle of repose, bulk density and tap density were used as the research objects to determine the most critical factors affecting the hygroscopicity of Polygonatum odoratum polysaccharide by stepwise regression method. The prepare tablet method was used to reduce the specific surface area based on the results of the stepwise regression method. In addition, the effects of tablet diameter, diluent and lubricant on the angle of repose, moisture absorption rate, hardness and fragility were investigated through single-factor experiments. On this basis, moisture-resistant intermediate tablets of Polygonatum odoratum polysaccharide were formulated using the Box-Behnken design-response surface method. The tablet's equilibrium moisture absorption rate and critical relative humidity were simultaneously determined and compared to Polygonatum odoratum polysaccharide powder. Results: The results of stepwise regression indicated that the specific surface area, bulk density, and content of protein, fructose, and other impurities in Polygonatum odoratum polysaccharide powder had significant effects on the powder's moisture absorption, with the specific surface area factor coefficient being the largest. The composition of the moisture-resistant intermediate tablets of Polygonatum odoratum was as follows: Lactose 17.00%, microcrystalline cellulose (MCC) 17.00% and magnesium stearate 0.80%. Compared to Polygonatum odoratum polysaccharide powder, the equilibrium moisture absorption rate decreased from 22.25% to 11.03%, and the critical relative humidity increased from 48.40% to 75.00%. Conclusion: Specific surface area was the main factor of moisture absorption of Polygonatum odoratum polysaccharide. Preparing Polygonatum odoratum polysaccharide powder into a moisture-resistant intermediate tablet could decrease its specific surface area, thereby reduce its hygroscopicity.