Abstract: Four main nutritional factors impacting the growth of Agaricus bisporus, including carbon, nitrogen, inorganic salt and vitamins, were studied via single- factor experiment, and the results showed the optimal carbon, nitrogen, inorganic salt and vitamin was soluble starch, peptone, KCl and VB1, respectively.The uniform design was employed to investigate the ratio between the optimal carbon, nitrogen, inorganic salt and vitamin of submerged fermentation of Agaricus bisporus, and the optimum medium was acquired: 4.6% soluble starch 4.6% peptone, 0.02% KCl and 18 mg /100 m L VB1. The optimized process of submerged fermentation of Agaricus bisporus via central composite experimental design and response surface analysis was obtained as follows: inoculum 11%, fermentation temperature 26℃ and rotation speed 143 r / min. The validation results of optimized process indicated the yield of dried Agaricus bisporus mycelium reached 3.125 g /100 m L and improved 202% compared with the unoptimized process.