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Unreasonable cultivation methods and management measures have led to widespread obstacles in tobacco continuous cropping in planting areas, resulting in reduced tobacco yield and soil degradation. Therefore, intercropping tobacco with other crops is an effective strategy to improve continuous cropping barriers. In this study, flue-cured tobacco NC102 and conventional planting varieties of Salvia miltiorrhiza were used as materials, and four treatments of flue-cured tobacco monoculture (CK), flue-cured tobacco, and Salvia miltiorrhiza at a ratio of 1:1 (TS11), 2:2 (TS22), and 2:3 (TS23), respectively, were set up to study their effects on soil microorganisms, physical and chemical properties, and yield and quality of flue-cured tobacco. The results showed that intercropping Salvia miltiorrhiza increased the number of soil bacteria and actinomycetes, decreased the number of fungi, and increased the activity of urease and sucrase. The content of available nitrogen and available phosphorus in intercropping Salvia miltiorrhiza soil was significantly higher than that of the flue-cured tobacco monoculture, while the content of available potassium was lower than that of the flue-cured tobacco monoculture. The soil environment was more conducive to the growth of flue-cured tobacco. Compared with the flue-cured tobacco monoculture, the proportion of superior tobacco in intercropping Salvia miltiorrhiza increased by 2.2–3.4%, and the ratio of potassium to chlorine in leaves of different parts of flue-cured tobacco increased by 12.3–75.0%. The content of total sugar and soluble sugar in middle and upper leaves of intercropping flue-cured tobacco was higher than that of the flue-cured tobacco monoculture, which improved the quality of flue-cured tobacco. From the analysis of the chemical composition of tobacco leaves, TS11 (flue-cured tobacco and Salvia miltiorrhiza intercropping row ratio of 1:1) had the best treatment effect, potassium content, total sugar, reducing sugar content, and potassium chloride ratio of flue-cured tobacco were the highest, the chlorine content was the lowest, and the quality was better than other treatments. From the analysis of total output value, the total output value of TS22 (flue-cured tobacco and Salvia miltiorrhiza intercropping row ratio of 2:2) was higher than that of other intercropping treatments. In 2018 and 2019, the total output value increased by 21.3% and 22.4%, respectively, compared with the flue-cured tobacco monoculture. The intercropping advantage was obvious, and the treatment effect was the best. [ABSTRACT FROM AUTHOR]