Abstract: In this study,the tilapia skin was as the raw material,and the lipase was used to remove fat from tilapia skin. On the basis of single-factor experiments,Box-Behnken central composite design combined with response surface methodology(RSM) was utilized to optimize the defatted conditions of tilapia skin. Three variables(defatted temperature,defatted time and enzyme dosage) were involved in this experiment,and the defatted rate was as the measure indicator. The results showed that the optimum defatted conditions for tilapia skin were pH9,enzyme dosage 0.5%,temperature 39 ℃,and defatted time 56 min. The defatted rate at this condition could reach 63.71%.