In order to explore the effects of nitrogen reduction conditions (21.49% reduction compared to traditional nitrogen application) combined with microbial agents on the yield and quality of flue-cured tobacco, the growth characteristic, chemical composition, sensory quality and economic effects of flue-cured tobacco were studied by double factors test considering fertilization model and microbial agents, and the contribution rate of fertilization mode, microbial agents and their interactions on the yield and quality of flue-cured tobacco was analyzed by η2 value. The results showed that nitrogen reduction fertilization combined with microbial agents can improve the physical properties of middle and upper tobacco leaves, the sugar content in upper, middle, and lower leaves of tobacco and the potassium content in upper leaves of tobacco increased by 15.47%, 9.03%, 81.41%, and 16.28%, respectively; the sensory quality of upper, middle, and lower tobacco leaves increased by 5.92%, 6.93% and7.36%, respectively; the proportion of positive group tobacco increased by 10.75% and the proportion of green and miscellaneous tobacco decreased by 55.35%;the partial productivity of nitrogen fertilizer and partial production efficiency of nitrogen fertilizer increased by 20.31% and 32.95%, respectively. The contribution rates of nitrogen reduction fertilization models, microbial agents, and the interactions to the growth characteristic of flue-cured tobacco were 37.25%, 38.83% and 23.92%, respectively; the contribution rates on chemical components were 39.04%, 31.64% and 29.32%, respectively; the contribution rates on sensory quality were 54.48%, 39.26% and 6.26%, respectively; and the contribution rates on economic character were 37.57%, 32.52% and 29.91%, respectively.