Southern Xinjiang region represents a prototypical oasis agricultural area, and cotton is the primary cash crop. The current cotton water productivity for this area remains room for improvement. In order to refine cotton drip irrigation strategy in Southern Xinjiang, this study combined field experiment with crop model simulation and prediction. In this experiment, two irrigation methods, furrow irrigation and drip irrigation, and different degrees of deficit irrigation were set up. The impacts of soil moisture on cotton yield and quality were assessed, with the additional utilization of the Root Zone Water Quality Model (RZWQM2) for simulating irrigation scenarios and predicting cotton yield field data showed that during the 2021–2022 growing season, drip irrigation significantly increased boll weight, yield, and Water Productivity compared to furrow irrigation. The deficit irrigation with 90 % of full irrigation during the flowering period resulted in the highest yield among all drip irrigation treatments, while simultaneously improving the fiber quality. The RZWQM2 model was calibrated and validated using 2021 and 2022 cotton field experimental data, respectively. The calibrated and verified RZWQM2 model shows good performance. In terms of soil water storage, cotton yield and evapotranspiration. The simulated value output by the model is close to the measured value in the field. Model prediction data suggest that there is still room for improvement in cotton yield, accompanied by an increase in evapotranspiration. But deficit irrigation below 80 % of the full irrigation quotas poses a notable risk of yield reduction. Targeting higher yields, the predicted scenario suggests an increase in water application (irrigation quota:314.8 mm). Additionally, this study proposes irrigation regimes with water savings of 10 % and 20 %, with irrigation quotas of 290.5 mm and 266.5 mm during the growth period, respectively. Based on this study, we provide a more detailed and reliable water-saving scheme for cotton drip irrigation in southern Xinjiang region.