Pot experiments were conducted in Yunnan Province of China. Six different treatments with mixed chemical and cake fertilizers, included no fertilization (CK), cake fertilizers only (100M), 75% organic manure and 25% chemical fertilizers (75M＋25F), 50% organic manure and 50% chemical fertilizers (50M＋50F), 25% organic manure and 75% chemical fertilizers (25M＋70F) with their replications and N, P and K chemical fertilizers only (100F) were examined．N application rate was the same in all the treatments (except no fertilization in CK). The effects of the fertilization modes on flue-cured tobacco, as well as nitrogen, phosphorus and potassium accumulation, losses of N and P were investigated. The results showed that application of cake fertilizers fermented could promote the growth of flue-cured tobacco plant, enhance leaf yield, increase ratio of high quality and economic benefits level leaves, while no fertilization resulted in soil fertility degeneration. There was a significant increase of soil fertility with balanced fertilization while cake fertilizers application combined with chemical fertilizers increased soil fertility most. Both the concentrations of N and P in different treatments decreased first and then increased during the whole growing period. At the same applied amount of N fertilizer, soil nitrogen leakage amount decreased with the increase of the ratio of cake fertilizers applied, but the more proportion of cake fertilizers, the higher accumulative leaching amount of P in leacheate. Based on the point of flue-cured tobacco growth and environment protection consideration, 1︰1 of organic nitrogen/inorganic nitrogen was recommended in the flue-cured tobacco fertilization.