Abstract: Abstract: Slightly saline water can be an important way to alleviate the current contradiction between the water supply and the demand in the Xinjiang irrigation area, particularly for the sustainable development of the local cotton industry. In this study, a systematic estimation was made to clarify the effects of different combinations of the amount (I) and electrical conductivity (EI) of irrigation water on the yields and profits of cotton. A two-year field experiment was also carried out under film-mulched drip irrigation in the nine experimental sites. Some indicators were then collected, including the data regarding soil (e.g. soil texture and bulk density), crop (e.g. cotton yield), and irrigation management (e.g. I and EI). The applicability and reliability were then verified on a biological-physical model-ANSWER (ANalytical Salt WatER) in the cotton yield. Combined with the Break-even method, The ANSWER was applied to investigate and evaluate the effects of different combinations of I and EI on the yield and profit of cotton using scenario analysis. Three statistical indices were employed to evaluate the performance of the model, such as the determination coefficient (R2), root mean squared error (RMSE) and relative root mean squared error (RRMSE). The results show that the ANSWER fully estimated the relative yields of cotton in the different experimental sites and irrigation treatments with the various levels of I and/or EI. The R2 values between the simulated and measured relative yields were consistently greater than 0.54, while the RMSE and RRMSE were not more than 0.14 and 0.16, respectively. There were relatively small differences in the optimized values of each biological parameter in the ANSWER (representing the physiological response of crop root water uptake to water-salinity stresses) among all experimental sites, with the absolute Coefficients of Variation (CV) value ranging from 0.08 to 0.37 and a mean of 0.19. An individual parameter presented a large degree of variation (i.e. CV = 0.37), but little sensitivity for the estimation of relative yield. Furthermore, the combination of the mean (MN) of originally optimized biological parameters for different experimental sites was also used to estimate the relative yields of cotton for each specific experimental site. The estimated results were comparable to the measurements, with an R2 of 0.59, an RMSE of 0.06, and an RRMSE of 0.07. Scenario analysis showed that the cotton profit first increased and then decreased with increasing I under a given EI, and that the I required for reaching or being close to the maximum profit at least increased rapidly with increasing EI. When the EI was limited to 10 dS/m, the resulting profit by saline water irrigation still shared the potential to approach or even exceed the level of profit resulting from the freshwater irrigation only by means of sufficient saline water replenishment. However, when the EI was above 15 dS/m, there was no profit, due to the excessive salt stress induced by the low yield. Moreover, if a relative yield of 0.80 was desired or expected, the EI should be set to less than 17 dS/m, and meanwhile, the relative irrigation amount (Ir) should be set to larger than 0.8. Overall, the Ir linked to the peak value of profit can be expected to serve as an appropriate value of irrigation amount to guide the irrigation management under a specific EI, in order to balance the relationships of high profit, water-saving, and sustainable use of saline water. By contrast, it is very necessary to provide some measures (e.g. physical, chemical, or biological) for the soil salt removal or reduction to avoid or relieve the excessive accumulation in the root zone. The finding can also provide the theoretical basis to evaluate the cotton yield and profit in the rational development and utilization of saline water resources in Xinjiang of Western China.