Abstract: On the basis of single factor experiments, orthogonal experiments were used to optimize the medium and culture conditions, and microencapsulation culture method was combined to achieve high density culture of Saccharomyces cerevisiae FM-S-115.Results showed that, by optimizing seven conditions of carbon source and carbon source content, nitrogen source and nitrogen source content, temperature, pH and inoculum concentration, single factor experiment determined the three most significant factors:Temperature, pH and carbon source content. Through the orthogonal experiment of three factors and three levels, the optimum culture conditions was determined:Temperature was 32℃, pH was 4.5, carbon source was sucrose and the content was 16%. Under this culture condition, the total number of colonies was 1.79×10⁸ CFU/mL, which was 1.75 times of the colony number of 1.02×10⁸ CFU/mL under normal culture condition. By measuring the capsule breaking rate of microcapsules prepared by sodium alginate and calcium chloride with different mass concentrations, the capsule damage rate was the smallest when the mass concentration of sodium alginate was 1.2% and the mass concentration of calcium chloride was 7%. FM-S-115 in microencapsulation cultured four generations under the optimal conditions for static, the total number of colonies was 8.10×10⁸ CFU/g, which was 7.94 times that of normal culture and 4.53 times that of culture under the optimal conditions. The cell density was greatly improved.