Abstract: Devosia sp. is a new microbial strain which can effectively remove deoxynivalenol(DON) from grain and feed. Its transformation product is a safe transformation product of deoxynivalenol. Based on the single factor experiments of carbon and nitrogen sources,eight factors including yeast extract powder,yeast extract,sucrose,potassium dihydrogen phosphate,ammonium sulfate,magnesium sulfate,calcium chloride,manganese sulfate and ferrous sulfate were selected to carry out partial factor experiment(FFD). Three most significant factors including yeast extract powder,yeast extract and sucrose were selected for steepest climbing experiment and response surface experiment. The optimum composition of fermentation medium was yeast extract powder 10.00 g/L,yeast extract 6.49 g/L,sucrose 8.40 g/L,ammonium sulfate 2 g/L,potassium dihydrogen phosphate 2 g/L,magnesium sulfate 0.7 g/L,calcium chloride 0.02 g/L and ferrous sulfate 0.02 g/L. Using this medium for fermentation verification test,OD₆₀₀ reached 21.66 in 40 hours,which basically accorded with the predicted value(21.62). In summary,the regression model was feasible to optimize the fermentation medium of Devosia sp.,and the biomass of the optimized medium increased by 89.1% compared with the original medium. Meanwhile,the cost was reduced simultaneously which laid a foundation for the industrial production of Devosia sp.