Abstract: Brackish water irrigation effectively alleviates the shortage of freshwater resources in arid areas. This study aims to explore the salt accumulation of cotton mulched drip irrigation with different salinity, together with their impact on crop growth. Taking the cotton (Nongfeng NO.133) planted in the test pit as a research object, a field test was conducted in the Key Laboratory of Modern Water-Saving Irrigation Corps (85°59ʹ47ʺE, and 44°19ʹ26ʺN). The size of the test pit was 2 m×2 m×2 m, where the bottom was set with a 30 cm sand and gravel filtration layer, and a cutoff wall was separated from the surrounding area. The cotton planting pattern was “one film, two pipes, and four rows” with a planting distance of 10 cm. The drip irrigation belt was laid between two narrow rows using the polyethene resin inlaid thin-walled maze (Xinjiang Tianye Water-Saving Irrigation Co. LTD). The drip head flow rate was 2 L/h. Two-year test pits of mulched drip irrigation were carried out with different gradient salinity. The irrigation water source was manually configured, according to the groundwater composition in the study area. The chemical mass ratio was NaHCO3:Na2SO4:NaCl:CaCl2:MgCl2=1:7:8:1:1. The selected fertilization level was 300-105-45 kg/hm2 (N-P2O5-K2O), the irrigation quota was 4800 m3/hm2, and the emerging water was fresh water. A total of six treatments were set with the salinity of 1, 2, 3, 4, 5, and 6 g/L. Some parameters were measured, including the soil electrical conductivity, cotton plant height, stem diameter, leaf area, aboveground biomass, and yield. An analysis was made on the salt accumulation characteristics of different soil layers during the cotton growth period. The AquaCrop model was constructed for the drip irrigation of the cotton under the water source film with different salinity using the data of local meteorology, soil, crop, management, and irrigation system. The results show that: 1) Soil electrical conductivity was positively correlated with the irrigation water salinity. The salt accumulation reached the peak in the 40-60 cm soil layer, whereas, there was less salt accumulation in the 80-100 cm soil layer. At the end of two years, the electrical conductivity was 3.03 and 3.15 dS/m, respectively, and the salt accumulation rate were 43.03% and 40.94%. 2) The maximum growth indexes and the cotton yield reached the mineralization degree of 3 g/L. There was no influence on the growth indexes and yield of 4 g/L, compared with the 1 g/L. An optimal irrigation water source was achieved between 3 and 4 g/L for the cotton. 3) A systematic evaluation was made on the simulated and measured values of canopy coverage and aboveground dry matter mass. Specifically, the R2 was greater than 0.812, while the root mean square error, standard root mean square error, and the consistent index value were less than 57.1, 24.1, and 0.998, respectively. The relative error was no more than 9.28% between the simulated value and the measured value of cotton yield, indicating excellent simulation. The AquaCrop model can be expected to better simulate the dynamic changes of canopy coverage, biomass, and yield during the growth and development of cotton mulched drip irrigation with different salinity, particularly for yield prediction and optimal management. The finding can provide a fundamental basis for the sustainable utilization of mulched drip irrigation with the saltwater resources in arid areas.