Abstract: By studying the effects of flue-cured tobacco intercropping patterns with different varieties and density combinations on soil nutrients, enzyme activities and economic traits, the following treatments were set up including A₁B₁ (flue-cured tobacco-chives: 3~5 cm/plant), A₁B₂ (flue-cured tobacco-chives: 6~10 cm/plant), A₂B₁ (flue-cured tobacco-endive: 20 cm/plant), A₂B₂ (flue-cured tobacco-endive: 40 cm/plant) and CK (flue-cured tobacco monoculture). The results showed that intercropping significantly increased the content of soil available potassium and organic matter, and the organic matter content of all intercropping treatments increased compared with flue-cured tobacco monoculture after 90 days of transplanting. the alkali hydrolyzable nitrogen content of A₂B₂ treatment significantly increased. Intercropping treatment has a significant effect on soil enzyme activity. A₂B₂ treatment significantly increased the activities of urease, sucrase, catalase and neutral phosphatase at 60 days of transplanting, and two-way ANOVA showed that available potassium, organic matter changes and soil enzyme activities were significantly dominated by the interaction between variety and density. The yield and output value per mu of A₂B₁ treatment were the highest, which were 70.2% and 76.9% higher than those of CK, respectively, and the interaction effect of variety and density had a significant impact on the yield and output value. In conclusion, A₂B₁ treatment could effectively improve the soil microenvironment and enhance the economic benefits of flue-cured tobacco, and provide a practical reference for the optimization of intercropping mode.