Ustiloxins are the main secondary metabolites of smutas. With the development of new varieties of rice and changes in the climate and environment, the diseases caused by them have expanded from accidental cases to cases worldwide. This affects the yield and quality of rice and has a significant impact on the growth and development of people and animals. The harm to human health caused by Ustiloxins needs to be further investigated. Therefore, to investigate the potential risk of ustiloxin's effects on human health, this study was conducted orally in male mice. Observation of morphological changes in cells and structural lesions of mitochondria using electron microscopy of HE staining and transmission. We combined transcriptomics, proteomics, and bioinformatics techniques to analyse the main objectives and regulatory networks of Ustiloxins in the case of liver damage to study the mechanism of liver damage caused by Ustiloxins in mice. The genes that were most differentially expressed were associated with terms such as "metabolism of exogenous substances with cytochrome P450", "peroxisomes and "negative regulation of the inflammatory response". Western blot and qRT‒PCR have shown that Ustiloxins can further activate the inflammatory pathways of Nrf2/HO-1 and NLRP3 by activating CYP450 to cause liver damage in mice.