<p>Colon cancer is one of the leading causes of cancer-related mortality, with liver metastasis commonly complicating its progression and significantly worsening patient prognosis. This study aims to explore the relationship between liver metastasis in colon cancer and various clinicopathological factors, as well as to investigate the underlying molecular mechanisms. The clinical data and weighted gene co-expression network analysis (WGCNA) were used to identify key genes associated with liver metastasis. The results revealed significant alterations in lipid metabolism associated with colon cancer progression. Notably, WGCNA and machine learning algorithms identified cardiolipin synthase 1 (CRLS1) as a hub gene robustly associated with liver metastasis in colon cancer. The expression of CRLS1 was assessed via scRNA-seq and the collection of clinical samples from colon cancer patients. CRLS1 knockdown significantly inhibited the proliferation and migration of colon cancer cells and suppressed lipid metabolism. Finally, several candidate drugs have been identified that may effectively target CRLS1. Moreover, it has been confirmed that the mTOR signaling pathway regulates CRLS1 expression, offering a promising avenue for future therapeutic strategies. In conclusion, this study highlights the pivotal role of CRLS1 in colon cancer and its potential as a biomarker and therapeutic target through lipid metabolism in managing this aggressive disease. </p>