Abstract This study aimed at guiding fertilizer management for Bt cotton cultivar SCRC28 growing in coastal saline soil in the Yellow River Delta area in Shandong Province, China. SCRC28 was planted in the soils with high, middle, and low salinity under 3 fertilizer treatments, namely control (no fertilizers), NPK, NP, and NK. The effects of different fertilization treatments on nutrient assimilation, Na + assimilation, net photosynthetic rate ( P n), dry matter accumulation, and lint yield of Bt cotton were investigated. Compared to the corresponding controls, the NP and NPK treatments had significantly higher nutrient uptake levels in plants in the 3 types of saline soils, and significantly lower levels of Na + uptake, especially the NPK treatment. The nutrient use efficiencies in agronomy of cotton in the NPK treatment were the highest among treatments regardless the salinity level. The N use efficiencies in agronomy were 0.20, 1.95, and 2.07 kg lint kg −1 under the low, middle, and high salinity level, respectively; the P use efficiencies in agronomy were 0.87, 8.35, and 8.71 kg lint kg −1, respectively; and the K use efficiencies in agronomy were 0.26, 2.89, and 3.77 kg lint kg −1, respectively. The NPK treatment also maintained the highest levels of leaf area, chlorophyll content, and P n among fertilization treatments in the 3 types of saline soils. The NPK treatment obtained the highest biomass and lint yield among the treatments, and the link yields were enhanced, compared to the corresponding controls, by 2.53%, 28.67%, and 30.47% in the low, middle, and high salinity soils, respectively. The effect of fertilization was obviously in the middle or high salinity fields. In this study, the fertilization quantities were based on the salinity level of soil. The NPK treatments were applied with N 165 kg ha −1 plus P 2O 5 38.57 kg ha −1 plus K 2O 111.5 kg ha −1 in the middle salinity soil and N 135 kg ha −1 plus P 2O 5 32.14 kg ha −1 plus K 2O 74.35 kg ha −1 in the high salinity soil. Therefore, rational fertilization schemes are recommended according to the salinity level of soil in order to alleviate nutrition obstacles and improve cotton nutrition, which ultimately result in the increases of nutrient use efficiencies in agronomy and cotton yield.