Abstract: Autolysis-ultrasonic coupling method was adopted to extract β- (1, 3) -D- glucan from waster beer yeast. Firstly, single factor and orthogonal test were designed to study the effect of different autolysis promoters on yeast autolysis. The results showed that the mixture of 5% NaCl+1.5% ethyl acetate can effectively promote yeast autolysis. Furtherly, ultrasonic method was used to extract β-(1, 3)-D-glucan from the cell wall deposition harvested after autolysis. The effects of ultrasonic power, ultrasonic time and ultrasonic times were explored in 2% NaOH solvent by response surface methodology. The results indicated that the optimum parameters were ultrasonic power 550 W, ultrasonic time 33 minutes, 2 ultrasonic times. Under the above conditions, the extraction rate of β-1, 3-glucan was up to 50.5 %, which was doubled as compared with pure ultrasonic method without autolysis pretreatment.