To investigate the mechanism of Bacillus amyloliquefaciens BLCC1-0238 in alleviating non-alcoholic fatty liver disease (NAFLD),a mice NAFLD model induced by a high-fat diet was established,and then low and high dose (106 or 108 CFU) B. amyloliquefaciens BLCC1-0238 was used to intervene. The protective effects of B. amyloliquefaciens BLCC1-0238 on the NAFLD mice were evaluated by examining physiochemical indexes in the serum and histopathological changes in the liver. The effects of B. amyloliquefaciens BLCC1-0238 on gut microbiota and hepatic lipid metabolism in the NAFLD mice were analyzed by genomics and transcriptomics,respectively. Quantitative reverse transcription PCR (qRT-PCR) was applied to verify the reliability of transcriptomics results. The results of physiochemical indexes showed that the levels of TC,TG,ALT,and AST were significantly reduced by B. amyloliquefaciens BLCC1-0238 intervention and the liver histopathological changes demonstrated that B. amyloliquefaciens BLCC1-0238 significantly reduced lipid deposition in hepatocytes. The results of genomic analysis showed that B. amyloliquefaciens BLCC1-0238 altered the microbial community structure in the gut,and significantly increased the relative abundance of Bifidobacteria,which produce short chain fatty acids. The liver transcriptomic analysis showed that B. amyloliquefaciens BLCC1-0238 was mainly involved in negative regulation of lipid metabolism pathways,such as fatty acid and cholesterol syntheses. Additionally,qRT-PCR confirmed the reliability of transcriptomic results. Collectively,B. amyloliquefaciensBLCC1-0238 can alleviate mice NAFLD by changing the microbial community structure in the gut and regulating hepatic lipid metabolism.