In this study, the formulation of Agaricus Blazei Murill polysaccharide effervescent tablets were optimized. The normalized values (Z) of effervescent tablets of disintegration time and friability was selected as the response value. The influence factors for formulation of Agaricus Blazei Murill polysaccharide effervescent tablets were acid and alkali mass ratio, Citric acid mass fraction, PEG6000 mass fraction. Moreover, a three-variable, five-level code experiment was designed to optimize the formulation of Agaricus Blazei Murill polysaccharide effervescent tablets. The quadratic polynomial regression equation was built and could well describe the relationship between the dependent and independent variables. The optimal formulation was as follows: 0.81 of mass ratio between acid and alkali, citric acid mass ratio 16.96%, and PEG6000 mass ratio 4.08%. Under these conditions, the disintegration time and the friability of the effervescent tablets were qualified, and the normalized values were close to the predicted values of the model. The newly developed formulation of Agaricus Blazei Murill polysaccharide effervescent tablets was feasible and effective.