Objective The circulating tumor cells(CTCs)are a key link of colorectal cancer(CRC)liver metastasis.However,there are still some limitations in the detection and reculture of isolated CTCs.Thus,novel markers are urgently needed to improve the detection of CTCs in blood from CRC patients.Methods The blood proteins secreted by CTCs that played an important role in liver metastasis of CRC were obtained through comprehensive bioinformatics analysis and the core genes were screened and validated by protein-protein interaction(PPI)network analysis and external gene expression omnibus(GEO)datasets.Results A total of four core genes secreted by CTCs that played an important role in CRC liver metastasis were identified,among which the apolipoprotein H(APOH)was the most important,and its expression was significantly higher in CTCs and liver metastases compared to primary colorectal tumors and other metastatic sites,and the CTCs also exhibited higher APOH expression levels than white blood cells in the blood.Receiver operating characteristic curve analysis showed that APOH had better diagnostic efficacy for CRC liver metastases.EHT1864,Lisitinib and Oxaliplatin were predicted as potential therapeutic drugs for CRC patients based on APOH.Conclusion APOH is a core gene secreted by CTCs and plays an important role in CRC liver metastasis.