The invention discloses a set fertilizer suitable for simplified and reduced fertilizer application of direct-sowing cotton and a fertilizer application method. The set fertilizer comprises a base fertilizer for one-time seed and fertilizer simultaneous sowing, a water-soluble fertilizer subjected to foliage spraying in the seedling bud stage-initial flowering stage and a water-soluble fertilizer subjected to foliage spraying in the flowering and boll-forming stage. Effective elements and pure nutrients of the base fertilizer for one-time seed and fertilizer simultaneous sowing comprise, by weight, 15-25% of N, 5-10% of P2O5, 15-25% of K2O and 3-5% of S. According to the formula of the water-soluble fertilizer subjected to foliage spraying in the seedling bud stage-initial flowering stage, the sum of concentrations of B and Zn is larger than or equal to 100 g/L, the ratio of the concentration of B to the concentration of Zn is 1:(1-2), amino acid is larger than or equal to 20 g/L, and amino-oligosaccharin is larger than or equal to 5 g/L. According to the formula of the water-soluble fertilizer subjected to foliage spraying in the flowering and boll-forming stage, the concentration of humic acid is larger than or equal to 30 g/L, the concentration of amino-oligosaccharin is larger than or equal to 5 g/L, the sum of concentration of N, P2O5 and K2O is larger than or equal to 200 g/L, and the ratio of the concentration of N to the concentration of P2O5 to the concentration of K2O is 2:1:2. By means of the set fertilizer, the requirement of cotton for nutrients in the whole growth and development stage can be effectively met, and the set fertilizer also has the functions of preventing diseases, preventing shedding of cotton buds and bolls, preventing boll rotting, resisting high temperature and the like; the fertilizer application procedure is simplified, the use amount of the chemical fertilizer is reduced, the utilization rate of the fertilizer is increased, and the fertilizer application benefit is increased.