Abstract: To optimize the cell autolysis processing of Debaryomyces hansenii cultured in monosodium glutamate waste water, the response surface methodology was used in this study.The cell lysis rate was considered as response value of the response surface methodology, which was based on single factors experiment of time, temperature p H and cosolvent. The obtained optimal conditions were time 23 h, temperature 54 ℃, pH5.5, papain 0.8%.Under the condition, the content of amino acid nitrogen in the yeast cell lysis solution was 14.76 g/L, which was close to the predicted optimal value 14.84 g/L. The model was reliable and the strategy for optimization of yeast cell autolysis was feasible, which could be applicable for guiding production practices.