A water-soluble polysaccharide from lily bulbs was isolated and purified by Saccharomyces cerevisiae fermentation. Proteins present in lily bulb extract were removed by extracellular proteases secreted by S. cerevisiae during fermentation. This novel method differs from traditional protein removal methods. A suitable yeast strain was selected. Culture conditions were optimized. Response surface methodology (RSM) was utilized to evaluate the effects of variables on the lily polysaccharide (LP) yield and the protein removal ratio (PRR). The results of applying RSM revealed that the optimum fermentation conditions were 87.5 g L-1 lily bulb powder, pH 5.6, and temperature 27.9 degrees C. When lily bulb extract was cultured with S. cerevisae under optimum conditions, the LP yield and the PRR were 6.56% and 91.46%, respectively. These values are in close agreement with the value predicted by the model. The resulting LP curding was further purified by DEAE Sepharose Fast Flow chromatography after isolation by alcohol precipitation post-fermentation. DEAE chromatography resulted in a fraction, LP-1 (yield: 4.46%) with a molecular weight of 65.0 kDa. LP-1 consisted of glucose and mannose in a molar ratio of 1:1.2. (C) 2014 Elsevier Ltd. All rights reserved.