To increase the dissolution ratio of waste activated sludge (WAS), which contributes to the post bio-treatment, the thermal alkaline pretreatment was applied and the optimization of operational parameters for enhanced acidification performance of WAS by thermal alkaline pretreatment was studied using response surface methodology. Mesophilic anaerobic fermentation experiment of pretreated WAS was conducted. Experimental results showed that temperature, pH and treatment time had significant influence on lysis rate of WAS and the maximum lysis rate of 48.10％ was predicted when the operational parameters were temperature 88.83 ℃, pH 12.0 and treatment time 73.79 min, respectively. After thermal alkaline pretreatment, the lysis rate, solute protein and carbohydrate concentrations were all apparently higher than those of untreated sludge (blank test). The maximum amount of volatile fatty acids (VFAs) was 3 269.20 mg/L in the thermal alkaline pretreated test on day 3, which was 3.22-fold of that in the blank test. VFAs composition analysis revealed that acetic acid was consistently most abundant, followed by n-butyric acid and iso-valeric acid in the pretreated test, while the order was changed to n-butyric acid> acetic acid> propionic acid in the blank test.