In order to get optimal fertilization model for cotton planting in saline-alkali soil, a field experiment was conducted in a moderate saline-alkali soil in Dongying, Shandong Province. Six fertilization treatments (including control without fertilization, conventional fertilization, optimized fertilization, one-time fertilization, chemical fertilizer reduction, chemical fertilizer reduction + organic fertilizer) were set up. The nutrient accumulation and yield of cotton were studied by sampling and analyzing the plant during the key growth periods. Results showed that compared with optimized fertilization treatment, dry matter yield and the nutrient contents of nitrogen and phosphorus in the organs for the one-time fertilization treatment were significantly increased. The total accumulations of nitrogen and phosphorus in the boll stage of one-time fertilization treatment were 23.39% and 13.97% higher than those of optimized fertilization treatment, respectively. Furthermore, these two increasing rates were 50.98% and 46.94% respectively compared with control. The treatment of chemical fertilizer reduction (N, P₂O₅, K₂O reduced 20%) + organic fertilizer had the highest cotton yield, which was 31.14% higher than control, 13.37% higher than conventional fertilization treatment, and the economic benefit was 1 925 Yuan/hm² higher than conventional fertilization. Cotton yield of one-time fertilization treatment was similar to that of custom fertilization treatment, and economic benefit was 279 Yuan/hm² higher than conventional fertilization Cotton yields were positively correlated with the contents of soil alkaline hydrolysable nitrogen and available phosphorus. In the moderate coastal saline soil, the chemical fertilizer reduction (N, P₂O₅, K₂O reduced 20%) + organic fertilizer and one-time fertilization measures would give the better performance in cost-saving and yield-increasing.