Colorectal liver metastasis (CRLM) is a major cause of mortality in colorectal cancer (CRC) patients, but its precise etiology remains unclear. Identifying genes associated with CRLM and understanding their molecular mechanisms is crucial. Here, we identified SERPING1 as a hub gene causing CRLM by WGCNA, differentially expressed genes analysis and K-M survival analysis. In addition, we confirmed the high expression of SERPING1 in CRLM using human samples. Furthermore, our in vitro experiments showed that SERPING1 promotes the proliferation, migration and invasion of human CRLM cells and activates the EMT pathway in human CRLM cells. Finally, to explore the role of SERPING1 in tumour microenvironment, we performed single-cell sequencing analysis and found that SERPING1 was enriched in cancer-associated fibroblasts (CAFs) and associated with immune infiltration of CAFs. Collectively, these studies identified SERPING1 as a promising target for the control of CRLM.