At present, the formulation of the irrigation quota of cotton under film drip irrigation condition is still based on the field irrigation experiments, while there are few studies on determining the irrigation quota of cotton under film drip irrigation condition by considering the soil moisture content during sowing time or by modeling. Through the continuous field test of cotton field trials in the southern Xinjiang region in 2017 and 2018, the DSSAT-CROPGRO-Cotton model was parameter calibrated and verified by using the measured biomass, soil moisture contents, leaf area index and yield data of cotton flowering and maturity in 2017 and 2018, respectively. Under film drip irrigation condition, three cotton irrigation quota levels, 24mm, 30mm, and 36mm, were designed in the experiment. The validated DSSAT-CROPGRO-Cotton model was also used to simulate the growth and yield of under-membrane drip irrigated cotton under eight different initial soil moisture content conditions of 1.2θFC, 1.1θFC, θFC, 0.9θFC, 0.8θFC, 0.7θFC, 0.6θFC, and 0.5θFC (θFC is the field water holding rate). The results showed that the simulated values of cotton phenology, soil moisture contents, leaf area index and cotton yield were well agreed with the measured values after parameter calibrated and model verification, meeting the requirements of cotton simulation accuracy under film drip irrigation condition in the field. However, the simulated biomass values deviated obviously from the measured ones. At the same time, based on the verified DSSAT-CROPGRO-Cotton model, the yield and biomass of cotton were simulated under different conditions of initial soil moisture content and irrigation quota. The results showed that the maximum simulated yield and biomass of cotton corresponded to an initial soil moisture content of 0.8θFC~θFC. Accordingly, irrigation quota should be between 330mm and 396mm during cotton-growing period. The simulation results can be used for reference in the cotton planting and irrigation management in southern Xinjiang.