【Objective】 To establish and improve the optimal water and nitrogen input strategy of machine-picked cotton under mulched drip irrigation, thus realizing water saving, quality improvement and efficiency increase.【Methods】 Taking the cotton as the research object by the drip irrigation machine under the film, three irrigation levels (0, 168, 240 and 312 kg/hm2) and four nitrogen levels (3,000, 3,525 and 4,200 m3/hm2) were designed to study the response mechanism of plant height, stem diameter, SPAD, LAI and other combinations of water and nitrogen.【Results】 The results showed that the plant height, stem diameter, SPAD and leaf area index increased with the increase of nitrogen and irrigation amount, but the amount of nitrogen and water could reduce the stem diameter of cotton. When the amount of irrigation was consistent, the water consumption of no nitrogen treatment was significantly lower than that of nitrogen application, the water consumption of 240 kg/hm2 was the largest. But the water use efficiency of nitrogen treatment was higher than that of non nitrogen treatment, and when the amount of irrigation was 3,000 and 3,525 m3/hm2, the water use efficiency increases with the increase of nitrogen application. With the treatment of nitrogen application 168 kg/hm2, the increase in the amount of irrigation promoted the nitrogen productivity of the machine, with a high nitrogen application of 312 kg/hm2, and the amount of irrigation reduced the productivity of nitrogen fertilizer. When the amount of irrigation was 3,525 m3/hm2 and the amount of nitrogen application was 240 kg/hm2, the water production efficiency of the machine, the number of effective single plant, the weight of the single boll and the clothes were the highest, which was the suitable irrigation and fertilization system in the local area.【Conclusion】 Irrigation and nitrogen application has significant interaction action on growth, water use efficiency, nitrogen partial factor productivity and yield of machine-picked cotton. Comprehensively considering the three evaluation indexes of seed cotton yield, water and nitrogen utilization rate and the adaptability of machine-picked cotton, when the irrigation amount is 3,600-4,200 m3/hm2 and the nitrogen application amount is 160-312 kg/hm2, the seed cotton yield, WUE and PFPN can reach more than 80% of the maximum value at the same time, which is the most suitable water and nitrogen combination range for machine-picked cotton in the experimental study area.