Corn stalk pretreated with laccase-vanillin system was used to produce particleboard by hot pressing without adhesive. The objective of this study was to investigate the effects of vanillin concentration, laccase dosage and activation time on mechanical properties of corn-stalk-based particleboard. The test results were statistically analyzed and optimized by using response surface methodology ( RSM). A quadratic regression model was developed between the influencing factors and board performance. The results showed that activation time was the greatest dominant influencing factor for modulus of rupture (MOR) and internal bond (IB) strength,and second was laccase dosage. Modulus of elasticity (MOE) was prominently affected by vanillin concentration and some interactions among the influencing factors. The suggested optimal conditions were about 4 mmol/ L for vanillin concentration, 95 U/ mL for laccase dosage, and 150 min for activation time.