Abstract: Objective: Ganoderma Spores (GS) was used as raw material as the ultrasonic extraction as the main method and laccase wall-breaking method the secondary one to extract Ganoderic acid, the extraction factors affected the extraction ratio were optimized.Methods: Ultrasonic time, ultrasonic frequency, solvent and enzymolysis time were identified as the main factors from asonic time, ultrasonic frequency, solvent, solid-liquid ratio, enzyme amount, enzymolysis time, digestion temperature and p H which influenced the extraction ratio using experimental design of Placket-Burman (PB) by design-expert software.On this basis, the experimental design of Box-Behnken (BBD) and response surface analysis method was used for regression analysis.Results: When the ultrasonic time was 3.2 h, the solvent was 97% ethanol, ultrasonic frequency of 2 times, enzymolysis time for1.2 h, reached the highest extraction rate was 3.40%, and the extraction yield increased 1.4 times compared with the initial design.The extraction rate of ganoderma lucidum acid was increased greatly and the extraction time was shorten by the combined ues of cell wall disruption with lasscase and ultrasonic extraction.