To construct a corn liquid culture system suitable for the degradation of Zearalenone (ZEN) by Trichiorya detotoxin JD45, the culture medium composition was systematically optimized by single factor test, Plackett-Burman design, steepest climb test and Box-Behnken response surface method with the growth OD600 as the response value. The effects of temperature, pH and fermentation time on ZEN degradation were further evaluated. The results showed that corn starch dry powder, glucose and potassium dihydrogen phosphate were the key influencing factors, and the quadratic regression model was extremely significant, with F value of 716.66, R² of 0.9989, adjusted R² of 0.9975, and P=0.9147. The optimized medium formula was corn pulp dry powder 12.5 g, glucose 1.64 g, potassium dihydrogen phosphate 0.33 g, magnesium sulfate 0.05 g, and the inoculation amount was 5%. The verification results were highly consistent with the model prediction value. Under this system, 28 ℃ and pH=5 were more conducive to JD45 degradation of ZEN, and the degradation was faster in the first 3 days of fermentation. The study provides experimental basis for the biological attenuation treatment of contaminated corn pulp and the resource utilization of by-products.