The mixed fermentation process of enzymatic brown rice was optimized by the response surface method. In order to optimize the growth of Saccharomyces cerevisiae and Lactobacillus plantarum in short-term mixed fermented brown rice, the fermentation medium components of the traditional brown rice enzyme were optimized and the interaction between the constituent components was analyzed. Firstly, the main factors were analyzed by pre-experiemntal. The vital influencing factors of biomass, such as honey, brown rice and NaCl, were determined by Plackett-Burman test. The direction and step size of the steepest climbing test are set according to the three important factors effect intensity. Finally, the Box-Behnken test was used to design a 3-factor 3-level response surface analysis test. The optimum fermentation medium was honey 3.38 g/100 mL, brown rice 10.71 g/100 mL, NaCl 0.24 g/10 0mL, malt 0.25 g/100 mL, barley germ 0.5 g/100 mL, (NH₄)₂SO₄ is 0.5 g/100 mL, tea powder 0.025 g/100 mL. After cultivating with the above culture medium, viable count was 5.35×10⁷ CFU/mL, which was close to the prediction, and was 9.37 times as much as that of basic medium with 5.71×10⁶ CFU/mL.