Abstract: To improve the community structure of rhizosphere microorganism in tobacco-planting soils and alleviate bacterial wilt disease caused by soil pathogens, a field experiment was conducted to study the effects of organic fertilizers combined with reduced chemical fertilizers (ORF) and conventional chemical fertilizers (CKF) on tobacco rhizosphere microorganism, bacterial wilt disease incidence, and the yield and quality of tobacco leaves. The results showed that comparing with CKF, the treatment of ORF increased the numbers of bacterial, actinomyces and total microorganism in rhizosphere soils. However, the number of fungal, Ralstonia solanacearum and the percentage of R. solanacearum in the total amount of rhizosphere microorganism decreased, and the differences were statistically significant on the 55th and 75th days after transplanting. In addition, the average well color development (AWCD) and the utilization ability of various carbon sources increased, especially on the 75th day after transplanting. Simultaneously, the ORF treatment reduced the incidence and index of bacterial wilt disease at entire growth stages, and the differences were statistically significant on the 75th day after transplanting, reduced by 69.66% and 57.08% respectively. There were no significant difference in the yield and quality between the two treatments, but the rhizosphere soil environment of flue-cured tobacco had been significantly improved by the ORF treatment. Therefore, ORF improves the community structure of rhizosphere microorganism, and enhances the stability and disease suppression of soil microbial ecosystem. Furthermore, ORF promotes the qualities of soils and tobacco leaves and alleviates tobacco bacterial wilt disease damage caused by soil microorganism.