Abstract: Colorectal cancer (CRC) ranks among the most prevalent malignancies worldwide. Its pathogenesis is regulated by multifactorial interactions and marked by significant heterogeneity. In recent years, numerous studies have shown that cholesterol metabolism disorders play a crucial role in the key biological behaviors of CRC, such as its occurrence, proliferation, metastasis, and drug resistance, through multiple mechanisms such as energy supply, signal transduction regulation, and changes in the tumor microenvironment. This article systematically reviews preclinical research and clinical trial evidence targeting the cholesterol metabolism pathway and it focuses on evaluating the potential of artificial intelligence (AI) technology for integrating multi-omics data, discovering new biomarkers, and predicting treatment responses. Based on this, the article has deeply analyzed specific bottlenecks in the process of translating basic research findings on the regulatory mechanism of cholesterol metabolism into clinical applications in the field of translational medicine. By bridging this gap we aim to provide a more forward-looking theoretical framework and practical guidance for developing precise CRC medical solutions.