This paper aims to obtain the optimal drying process of Pleurotus ostreatus as well as to improve the quality of its drying products. Based on the methods of single factor and response surface method with the Box-Benhnken design (BBD), an experiment was conducted to analyze the effect of three factors including the microwave power, moisture content of switching point and vacuum freezing time on the 4 indicators of dry basis moisture content, drying rate, rehydration ratio and sensory score of the product correspondingly. The quadratic regression models of the 4 indicators were constructed and analyzed with the response surface method according to the experimental data, and the optimal drying process of Pleurotus ostreatus was obtained, which was microwave power 300 W, conversion point moisture content 37%, vacuum freezing time 11 h. In addition, the nutrients of the dried Pleurotus ostreatus (protein, crude fat and total sugar content) were measured under the optimal process conditions. From the experiment and data analysis, it can be concluded that under the proposed optimal processing, the dried Pleurotus ostreatus products have the advantages of good color, excellent quality and high retention of nutrients, which can guide the mass-production of dried Pleurotus ostreatus under industrial conditions.