The scientific gap of operating parameters of combined thermal and ultrasonic disintegration at low temperature of waste activated sludge (WAS) still needs to be filled. This study provides more insights into the technical feasibility of low organic WAS disruption pretreated by combined thermal at temperature lower than 100℃ and ultrasonic technique. Optimization of combined thermal and ultrasonic disintegration of WAS for enhanced organic releasing was carried out using response surface methodology (RSM) and Box-Behnken design of experiment. The quadratic effects as well as the interactive effects of temperature and specific energy on the disintegration degree of SCOD, soluble concentration of protein and carbohydrate were investigated. Results indicated that quadratic effect of temperature was more significant in affecting sludge disintegration than specific energy and regression models had good fitness with experimental results. The optimum disintegration degree of SCOD, soluble concentration of protein and carbohydrate achieved were 39.01%, 1360.59mg/L and 334.52mg/L, respectively, at 80℃ and 12000kJ/kg TS.In addition, the verification experiments appeared high coincide degree with predicted results, indicating that the models were reliable for application and promotion of combined thermal and ultrasonic disintegration.