In recent years, in order to control production costs, tobacco growers have simplified and changed the operation mode of fertilization technology in tobacco fields, resulting in various forms of fertilization and different effects. In order to verify the fertilization mode of tobacco farmers, and to screen out a set of optimized fertilization combination which can save labor, reduce cost and also guarantee the income, the orthogonal test method was used to carry out multi point experiment. The effects of different fertilizer application methods, basic fertilizer combination mode and compound fertilizer amount on the economic benefit of flue cured tobacco in Panzhihua tobacco planting area were studied. The results showed that the application mode of basal fertilizer was the main effect factor of the cost, and the basic fertilizer combination mode was the second. The effect of compound fertilizer dosage on cost was the smallest, and the "strip", "525 kg/hm2 compound fertilizer dosage" and "base fertilizer (compound fertilizer) + lift fertilizer (120 kg/hm2 chasing fertilizer I) + uncovering top box fertilizer (450 kg/hm2 recovery II). The cost is the lowest of three factors. But for the output value, net output value and input-output ratio, the basic fertilizer combination mode became the main effect factor of the effect index, followed by the application mode of base fertilizer, the effect of compound fertilizer dosage was the smallest, and the "circle application" and "base fertilizer (compound fertilizer) + lifting fertilizer (120 kg/hm2 fertilization I) + uncovering box Fertilizer (450 kg/hm2 top dressing II) has the best economic benefit. In comprehensive consideration, the best combination method of fertilization was "ring application base fertilizer (600 kg/hm2 compound fertilizer) + lifting fertilizer (120 kg/hm2 fertilization I) + top box fertilizer (450 kg/hm2 recovery II)". Under the present technical conditions, the economic benefit of the tobacco farmers' self adjustment and change of fertilization is not as good as the conventional three stage fertilization of "ring application base fertilizer + lifting fertilizer + uncovering box fertilizer", and the tobacco area should continue to be carried out according to the current fertilization technology.