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In this study, high-throughput sequencing (HTS) was used to compare and analyze the microbial diversity and variation law during the brewing process of xiaoqu Baijiu. The results showed that 34 phyla, 378 genera of bacteria and 4 phyla, 32 genera of fungi were detected. At the phylum level, Firmicutes, Proteobacteria, Bacteroidetes, Ascomycota and Bacteroidetes were the dominant groups. During the brewing process of xiaoqu Baijiu, the dominant bacteria were Weissella and unidentified Rickettsiales 2 days before brewing and Lactobacillus 3 days after brewing until the end of brewing. The dominant fungi were Rhizopus, Saccharomyces and Issatchenkia. The relative abundance of Rhizopus decreased with the extension of brewing time, while the relative abundance of Saccharomyces increased and became the dominant bacteria after the second day of brewing. This study revealed the diversity and variation of microbial community in the brewing process of xiaoqu Baijiu, and provide theoretical support and lay the foundation for future study on the contribution of microbial metabolism during brewing of xiaoqu Baijiu, thereby promote the development of xiaoqu baijiu industry.