The Ultraction-cellulase synergistic extraction process of pleurotus ostreatus polysaccharide (POP) was optimized by uniform design method. Extraction temperature, pH, solvent/material ratio, cellulase dosage, enzymolysis time, ultrasonic power and ultrasonic time were selected to carry out the single factor tests. According to the experimental results, better levels of these factors were chosen to implement the U₁₈ (9⁵×6²) mixed uniform design experiment to optimize the technology. The effects of the seven single factors as well as their interactions on the POP yield were investigated. The optimal process parameters were predicted and verified by using regression analysis. The optimal extraction conditions of POP were concluded as follows, i. e. extracting at 25 ℃, solvent/material ratio 22, pH 7.5, using 0.5% cellulase, enzymolyzed for 6 min, and ultrasonically treated for 69 min with 120 W. Under these conditions, the yield of the POP was up to (36.71±0.46) %. This optimized extraction process was feasible and effective.