To solve the issue of nitrogen out of limits in co-treatment of domestic wastewater and landfill leachate, numerical simulation was employed to build the mathematic model in A2O process based on activated sludge model ASM2d. On the analysis of sensitivity parameters and calibration parameters, the relative error between the simulated value and the measured value of COD, TN and NH4+–N in the effluent were 2.1%, 2.6% and 1.6%, respectively. The effects of different internal return ratio, sludge return ratio and the concentration of dissolved oxygen in the aerobic tank on nitrogen removal were also conducted by using single factor experiment and multi-factor orthogonal experiment. The results showed that the optimum removal efficiency could achieved in the 400% of internal return ratio, 100% of sludge return ratio and 3 mg/L concentration of dissolved oxygen in aerobic tank.