Colorectal cancer liver metastasis (CRCLM) is the primary cause of poor prognosis and mortality in patients with colorectal cancer (CRC). Aberrant protein expression and dysregulated signaling networks in tumor tissues are key drivers of CRCLM malignant proliferation and metastasis. As a crucial medium-chain fatty acid, octanoic acid exhibits potential regulatory effects on tumor biological behaviors and microenvironmental homeostasis. However, the systematic protein-level mechanism by which octanoic acid modulates CRCLM progression remains unclear. In this study, a well-established CRCLM mouse model was treated with octanoic acid intervention, and tumor tissues of liver metastatic lesions were collected for quantitative proteomic analysis. Differentially expressed proteins (deps) between the octanoic acid-treated group and the control group were screened, followed by functional enrichment analysis including gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathways to identify core regulatory proteins and key signaling pathways.