Abstract: Water scarcity and soil salinization have been limited to agricultural production in arid and semi-arid regions. For instance, the average annual precipitation in Xinjiang is only about 150 mm, but the annual evaporation exceeds 2 000 mm, where more than 94% of the available water resource is consumed by agriculture. Among them, one-third of arable land has experienced soil salinization. Furthermore, the degree and scale of salinization are ever-increasing each year. Therefore, there is a high demand to regulate the soil water and salt conditions in the root zone using irrigation scheduling. This study aims to promote the sustainable development of oasis agriculture in Xinjiang. The irrigation scheduling and quota were optimized to save water and regulate the soil salinity. A field experiment was conducted in Shawan City, Xinjiang, China in 2021 and 2022. The cotton was planted in the saline-alkali field and drip-irrigated under film mulch. The control treatment was selected as the local traditional irrigation scheduling. Smart irrigation was also implemented to evaluate the plant water deficit index (PWDI) over the treatment-designed threshold. The PWDI threshold was set at 0.62 and 0.50 in 2021 and 2022. Different salt leaching coefficients (1.0 and 2.0 in 2021; 1.0, 1.4, 1.8, 2.2, and 2.6 in 2022) were set to explore the effects of irrigation quota on soil water and salt transport, cotton growth, and water use. The irrigation quota was also determined, according to the soil water and salt conditions. In general, the irrigation quota increased for a constant PWDI threshold, when the salt leaching coefficient raised. The irrigation period was also prolonged, namely the irrigation frequency decreased. The total irrigation depth increased, where more salt was leached to the lower soil layer in the root zone or even out of the root zone, thereby improving the soil water and salt conditions. The water and salt stress were reduced to improve the cotton growth and yield while leading to a gradual decrease in the use efficiency of irrigation water. Once the salt leaching coefficient (irrigation quota) increased to the critical value, the long-term superior soil water and salt conditions in the root zone resulted in the overgrowth of cotton, namely, vigorous nutritional growth but delayed reproductive growth. Therefore, the irrigation period was shortened, and the total irrigation depth increased sharply, while the cotton yield decreased, leading to a significant decrease in the irrigation water use efficiency. The salt leaching coefficient of 2.2 was recommended for the cotton growth and yield, as well as water use efficiency. The PWDI threshold was set as 0.5 in the experimental area. Compared to 1.0, when the salt leaching coefficient was set as 2.2, the average irrigation quota increased from 42.5 to 85.0 mm during treatment period in 2022, the irrigation events decreased from 9 to 6 times, the total irrigation depth increased from 382.7 to 510.2 mm, more than 7.63 ×10³ kg/hm² salt was leached to the soil layer deeper than 100 cm, and the average PWDI decreased from 0.35 to 0.30, resulting in a 15.0% increase for yield and a 8.8% decrease for irrigation water use efficiency. The findings can provide the theoretical evidence and technical support to improve the smart irrigation of saline farmland, in order to promote the sustainable development of oasis agriculture in Xinjiang. The salt leaching efficiency can also be optimized to adopt the chemical amendment, according to the rooting depth during growth season.