To investigate the applicability of the AquaCrop model to drip-irrigated cotton without plastic film in South Xinjiang, and develop the optimal irrigation scheduling, the AquaCrop model was calibrated and validated by using the dataset collected in 2018 and 2019 seasons, then the model was used to simulate canopy cover (CC), plant biomass, and cotton yield under two different irrigation scenarios. The results showed that the root mean square error (RMSE), the fit index (d), the standard root mean square error (NRMSE) and the determination coefficient (R2) between the simulated and measured values of CC were 6.03%, 0.12, 13.08% and 0.97, and the corresponding values for plant biomass and cotton yield were 810kg/hm2, 0.93, 6.41% and 0.80, and 751kg/hm2, 0.84, 14.02% and 0.87, respectively, indicating that the AquaCrop model could be used as a feasible tool to predict cotton growth and yield response to irrigation under drip irrigation without plastic film in this region. The scenario simulation was carried out by using the AquaCrop model with the meteorological data from 1960 to 2019. The scenario simulation results indicated that under the condition of the same irrigation frequency, the cotton yield was increased first and then decreased with the increase of the irrigation quota, 〖JP3〗and the maximum yield of 5398kg/hm2 was obtained with the total irrigation amount of 7200m3/hm2, and the water use efficiency (WUE) was 0.75kg/m3. While under the condition of the same irrigation quota, the cotton yield was increased with the increase of irrigation frequency, and the maximum yield of 5315kg/hm2 was achieved with the irrigation frequency of 5d and the total irrigation amount of 5400m3/hm2, and WUE was 0.98kg/m3. It could be concluded that the high yield and WUE of drip-irrigated cotton without plastic film could be ensured by the irrigation scheduling with the irrigation frequency of 5d and the total irrigation amount of 5400m3/hm2, which could be used as a reference irrigation scheduling for application of drip-irrigated cotton without plastic film in South Xinjiang.