In order to clarify the regulation effects of enhanced density combined with reduced nitrogen fertilizer on yield, quality and fertilizer use efficiency of flue-cured tobacco, a field experiment which took flue-cured tobacco cultivar "Yunyan 105" was conducted in rainy areas for two years (2016 and 2018). Three plant densities (low density of 13 890 plants/hm², medium density of 15 150 plants/hm² and high density of 16 665 plants/hm²) and four nitrogen levels (0,84, 94.5 and 105 kg/hm²) were set, and the effects of planting density, reduced nitrogen and their interaction on yield, quality and nutrient use efficiency were studied. The results showed that compared with the conventional planting pattern, moderate density and reduced nitrogen fertilizer significantly promoted fertilizer use efficiency, yield and output, increased the contents of total sugar, reducing sugar and potassium, reduced total nitrogen and nicotine contents, but did not affect water-soluble chlorine significantly, resulting in the more harmonious tobacco chemical components. The chemical components usability index and NPK utilization in flue-cured tobacco were significantly affected by year, density, N application and their interactions, including the interaction of year and N rate, density and N rate, year both density and N rate. Meanwhile, the contribution of N fertilizer on chemical components usability and fertilizer use efficiency of flue-cured tobacco were 42.5%, 38.2%, and that of planting density were 27.3%, 25.4%, and that of the interaction of both planting density and N rate were 18.9%, 23.8%, respectively. Compared with the current cultivated pattern of flue-cured tobacco, the enhanced density combined with reduction of 10%~20% in nitrogen fertilizer significantly affected to yield, quality and NPK use efficiency of tobacco, and the optimal cultivated pattern of planting density and N rate should be 15 150 plants/hm² and 84.0~94.5 kg/hm², respectively.