Abstract: Protein arginine methylation is an important post-translational modification and epigenetic regulation mechanism. In mammalian cells, protein arginine methyltransferases (PRMTs) catalyze the methylation of protein arginine residues. Eleven PRMTs have been found in mammals and plants to date. PRMTs catalyze the transfer of methyl groups from S-adenosyl-L-methionine to the guanidinium nitrogen atom of arginine residues in substrates to produce arginine methylated proteins, thus playing key roles in the control of many biological processes such as DNA damage repair, RNA splicing processing, transcription, translation, cell signal transduction, cell cycle regulation, protein-protein interactions, protein-nucleic acid interactions. Dysregulation of protein arginine methylation mediated by PRMTs is closely related to the occurrence and development of cancer. Therefore, the development of anticancer drugs targeting PRMTs has also become a research hotspot in the field of cancer treatment. This paper reviews the role and molecular mechanisms of PRMTs in the pathological process of colorectal cancer, and introduces the research progress of small molecule drugs targeting PRMTs in colorectal cancer therapy, aiming to provide a theoretical basis and important clues for the development of small molecule drugs isolating from natural products and targeting at PRMTs in colorectal cancer treatment.