D380 resin utilized as a support for laccase immobilizationwhich applied to pollution degradation. Plackett-Burman design showed cross-linking temperature, immobilization pHand dilution ratioweremajor factors among cross-linker concentration, cross-linking temperature, cross-linking time, immobilization pH, enzyme dilution ratio, ion concentration, immobilization time, immobilization temperature and the consumption of enzyme. For further practical application in pollution degradation area, the optimized model conditions are needed. The mathematical model of optimized conditions was obtained through the regression equation of the response surface methodology. In this work, the optimum technological conditions were investigated as cross-linker concentration of 10%, cross-linking time of 2 h, cross-linking temperature of 31ï°c pH =7.2, enzyme dilution ratio of 900, consumption of enzyme of 10ml, PEB ion concentration of 0.2mol/L, immobilization time 6 h and immobilization temperature of 30 ï°c, respectively. Compared average immobilized enzyme activity 15.53U/g of the verification testwith theoretical value 15.95U/g, the results proved that themathematical model was feasible.