In 2021, 35 field experiments on the utilization efficiency of fertilizer (16 for maize and 19 for cotton) were conducted in the Southern Xinjiang region to study the effect of fertilization and the relationship between soil fertility and utilization efficiency of fertilizer in the Southern Xinjiang region. The nutrient deficiency treatments (NP, PK, NK) and full fertilizer treatment (NPK) were set up. The yield response, agronomic efficiency, nutrient accumulation pattern, soil fertility and the effect of fertilization on utilization efficiency of fertilizer for maize and cotton were studied respectively. Results showed that the average yield of maize and cotton treated with NPK was 14 020.3 kg/hm² and 6 582.7 kg/hm², respectively. The average agronomic efficiency of N, P₂O₅, K₂O was 13.0 kg/kg, 13.3 kg/kg, 10.7 kg/kg,and 6.1 kg/kg, 7.6 kg/kg, and 7.5 kg/kg, respectively. The average utilization efficiency of N, P and K fertilizers for maize and cotton was 42.4%, 21.2%, 54.1% and 41.7%, 18.9%, 58.2%, respectively. The application of N, P and K fertilizers increased yield of maize and cotton by 30.6%, 14.7%, 6.5% and 41.5%, 21.1%, 13.4%, respectively. Fertilizer application significantly improved the uptake of N, P and K by maize and cotton. 2.44 kg N, 0.91 kg P₂O₅, and 2.87 kg K₂O were required for every 100 kg maize kernels. 5.37 kg N, 1.67 kg P₂O₅, and 4.36 kg K₂O were required for every 100 kg cotton seed. The utilization efficiency of phosphorus fertilizer in maize was significantly and negatively correlated with the application of phosphorus fertilizer, and the utilization efficiency of phosphorus and potassium fertilizer in cotton was significantly and negatively correlated with the application of phosphorus and potassium fertilizer as well. Maize yield was negatively correlated with the application of phosphorus fertilizer and positively correlated with the content of effective phosphorus in soil, indicating that there may be a certain problem of excessive application of phosphorus fertilizer in maize in the Southern Xinjiang region. The utilization efficiency of potassium fertilizer in maize and cotton was significantly negatively correlated with the content of effective phosphorus in soil. There was a significant negative correlation between soil pH, cotton yield, and the utilization efficiency of nitrogen and phosphorus fertilizer in maize. It is indicated that soil salinity and alkalinity in the Southern Xinjiang region are one of the main limiting factors affecting cotton yield and the improvement of utilization efficiency of nitrogen and phosphorus fertilizer in maize. In the future, it is necessary to further optimize fertilization, increase the management of saline and alkali farmland, and improve utilization efficiency of fertilizer in combination with the popularization of drip irrigation technology in the Southern Xinjiang region.