TAM co-culture model, liver metastasis models and clinical tissue microarray (n=42) were used to validate the key secreted cellular factor and its associated receptor that mediated the interactions between SPP1<sup>+</sup>TAMs and CRC cells.<h4>Results</h4>We found that migration inhibitory factor (MIF) was the most important signaling molecule involved in the interaction between SPP1<sup>+</sup>TAMs and CRC cells, as revealed by cellular interaction analysis of integrated scRNA-seq datasets. This evidence concerns the gene MIF and colorectal carcinoma.