RAD52 plays crucial roles in several aspects of mammalian cells, including DNA double-strand breaks repair, viral infection, cancer development, and antibody class switching. To comprehensively elucidate the role of RAD52 in maintaining genome stability and uncover additional functions of RAD52 in mammals, we performed the transcriptomics and proteomics analysis of the liver of RAD52 knockout mice. Transcriptomics analysis reveals overexpression of mitochondrial genes in the liver of RAD52 knockout (RAD52KO) mice. Proteomics analysis of RAD52KO mice shows that damage recognition proteins Cul4b and Rad23a in the process of nucleotide excision repair pathway are overexpressed. Furthermore, gene ontology and KEGG enrichment analysis (accessed on 20 November 2024) from integrated omics shows that differentially expressed genes are significantly enriched in pathways related to mitochondrial oxidative phosphorylation and nucleotide metabolism in the liver of RAD52KO mice. In addition, mRNA and protein levels of Bhmt1b are elevated in the liver of RAD52KO mice. Taken together, this study provides valuable insights into the function and mechanism of RAD52.