In the present work, we investigated and optimized the digestion efficiency, A/S (Al2O3/SiO2 in red mud), and N/S (Na2O/SiO2 in red mud) of mixed bauxite in Iran Alumina Company using the Bayer process. Digestion experiments were carried out in an induction rotary autoclave on a mix of Jajarm, Yazd, Tash, and Shirin Cheshmeh bauxites. A 4-factor 3-level response surface methodology was applied for the design and analysis of the experiment with the optimization of Na2O concentration, digestion temperature, residence time, and amount of lime addition. Towquadratics and one linear model were derived for the prediction of digestion efficiency, and A/S and N/S responses. The results obtained showed that the optimum amounts for Na2O concentration, temperature, amount of lime addition and residence time were 180 g/L, 275°C, 7.73%, and 50 minutes, respectively, in which the digestion efficiency, A/S, and N/S reached 72.05%, 1.169, and 0.27, respectively. Validation experiment showed that the digestion efficiency, A/S, and N/S were 72.24%, 1.162, and 0.28% respectively, which meant a 2% increase in digestion efficiency and a 0.09 and 0.02 decrease in A/S and N/S, respectively, compared to the current operating condition.