In order to optimize target temperature, holding time and NaOH dose on solubilization degree of thickened waste activated sludge, a combined NaOH-microwave pretreatment process was studied on the basis of uniform design method. The results indicated that the variables markedly affected the solubilization degree of chemical oxygen demand (COD). The optimal conditions were determined and two-dimensional and tri-dimensional response surfaces were plotted according to the mathematical models. Within the design boundaries, the predicted maximum solubilization ratio of COD (80%) occurred at target temperature of 210°C, holding time of 51min, and NaOH dose of O.23g-NaOH/g-TSS. Under the optimal conditions, the experimental solubilization ratio of COD (82%) was in agreement with predicted value with 2.5% deviation.