Abstract: In order to improve the degree of hydrolysis of protein from tilapia scraps,in oculating Bacillus subtilis to tilapia scraps,the fermentations conditions of producing peptide with tilapia scraps were optimized by response surface experiments. Main factors that influenced degree of hydrolysis were identified by Plackett-Burman(PB)design,the optimal regions of the degree of hydrolysis were approached by the steepest ascent path,response surface experiments were analyzed by Box-Behnken design,and the molecular weight distribution of the peptide from tilapia scraps was determined by high performance size exclusion chromatography. The results of response surface experiments indicated that the optimal fermentation conditions for producing peptide with tilapia scraps was determined as tilapia scraps 13.8%,34℃,48.6 mL medium in 250 mL triangular flask. Under the optimal fermentation conditions,the degree of hydrolysis of protein from tilapia scraps was up to 33.12%.The result of high performance size exclusion chromatography showed that oligopeptide content reached up to 74.058%.