Abstract: Colorectal cancer, one of the most common malignant tumors worldwide, involves various complex pathophysiological processes. With the in-depth study of molecular science, weidentified lactylation, a new post-translational protein modification, as a key regulator in the initiation and progression of colorectal cancer. Lactylation refers to the modification of lysine residues in proteins by the addition of lactyl groups derived from lactic acid. As a glycolytic end product, lactate accumulates in the tumor microenvironment and regulates gene expression and cellular function by inducing lactylation of histone and non-histone proteins. This article describes how lactylation modification drives tumor immune evasion, metabolic reprogramming, and angiogenesis through epigenetic mechanisms, and elaborates on its impact on the occurrence, metastasis, and multidrug resistance in colon cancer.