[Objective] To optimize the nitrogen application system for drip irrigation cotton under reduced nitrogen fertilization. [Methods] Sampling field experiment and AquaCrop model were combined to carry out the study. [The results showed that the highest cotton yields of 5.496×103kg·hm2 and 5.126×103kg·hm2 were obtained from W2Nck (10% reduction in irrigation with normal N application) or W1Nck (10% increase in irrigation with normal N application) treatments, and the highest yields of 5.496 t·hm2 and 5.126 t·hm2 were obtained from W2N1 (10% reduction in irrigation with 30% reduction in N application) or W1N1 (10% increase in irrigation with 30% reduction in N application). 10% paired with 30% reduction in N application) treatments had the lowest cotton yields of 3.933×103kg·hm2 and 3.625×103kg·hm2, and the combined effect of water and nitrogen stresses negatively affected cotton yields; compared with single measures, increasing or decreasing the irrigation volume at normal nitrogen application levels could result in a yield-increasing effect; appropriately decreasing the irrigation volume or increasing the nitrogen application was more conducive to increasing the water use efficiency and reduce nitrogen residue in the soil. The AquaCrop model was calibrated with two years of experimental data, and the calibrated parameters were used to simulate cotton yield and water and nitrogen utilization under 300-600 mm irrigation quota under nitrogen reduction conditions 0.94; biomass evaluation index R2>0.947, NRMSE<40.58, ENS>0.72, yield evaluation index R2>0.91, NRMSE<4.29%, ENS>0.85; and water use efficiency evaluation index R2>0.87, NRMSE<4.22%, ENS>0.81, which indicated that the AquaCrop model had a better effect on the water-nitrogen treatment in cotton fields has good applicability. [Conclusion] Model simulation of 240 nitrogen and irrigation combinations, combined with the analysis of yield, water use efficiency and nitrogen bias productivity indexes, the combination of 10% nitrogen reduction and 360 mm irrigation quota can be used as a preferred solution to achieve stable yield and reduce economic costs under efficient water and nitrogen utilization. The optimization of cotton irrigation and nitrogen application system under the premise of stable yield of cotton under drip irrigation under membrane in Northern Xinjiang can be used as a reference basis for improving water and nitrogen utilization efficiency during cotton cultivation in arid areas.