Abstract: To illustrate the bacterial diversity of flue-cured tobacco K326 leaves during co-fermentation with three types of Qu used for Chinese rice wine fermentation, which are traditional wheat Qu, cooked wheat Qu, and Bai Qu, and to determine the influence of co-fermentation on the key enzyme activity, this study performed high throughput sequencing for analyzing the composition and dynamic changes of bacterial community during the co-fermentation process. The correlation between bacterial diversity changes and key enzyme activities in tobacco leaves was further explored. The results showed that the operational taxonomic units（OTU） of 10 g tobacco leaves samples co-fermented with three types of Qu were 103～344 OTU, and there was significant dif-ference among them. During the co-fermentation process, traditional wheat Qu treated tobacco leaves sample contained the most specific OTU, and the predominant genus in the traditional wheat Qu treated samples were Saccharopolyspora, Staphylococcus, and Pseudomonas. Compared with the other two co-fermented tobacco lea-ves samples, the Bai Qu treated sample had the highest richness and diversity, with the predominant genus of Weissella, Staphylococcus, and Pseudomonas. Compared with traditional wheat Qu and cooked wheat Qu, clu-ster analysis result showed that the co-fermented tobacco leaves with Bai Qu in different fermentation periods were not highly correlated, which suggested its high variability. Redundancy analysis further showed that the changes in the bacterial community were closely related to the variations of key enzymes activities in tobacco leaves, among which the amylase influenced the most of the core bacteria microbiome. The results of the pre-sent study would help to improve the quality of flue-cured tobacco leaves by applying of microbiological strains in the aging process of tobacco leaves.