Epigenetic modifications, such as alterations in DNA methylation patterns and histone changes, play critical roles in human disease. Since identification of protein arginine methyltransferases (PRMTs), arginine methylation has been largely recognized and is under robust investigation. During arginine methylation process, PRMTs transfer methyl groups from S-adenosylmethionine (SAM) to guanidine nitrogenes of specific arginine residues on their target proteins. After arginine methylation, protein structure, protein-protein interaction, protein localization and enzyme activity are changed. As a result, diverse cellular functions including signal transduction, RNA processing, DNA repair and gene transcription are under regulation of arginine methylation. Recently, emerging evidences have shown links between dysfunction of arginine methylation and cancers. In prostate cancer, H4R3 methylation by PRMT predicts the risk of cancer recurrence; in Mixed Lineage Leukaemia (MLL), PRMT mediates transcriptional upregulation during cancer progression. Moreover, aberrantly high expression of PRMT is observed in tumor tissues of both breast and colorectal cancer and, notably, is associated with poor clinical outcomes in colorectal cancer patients. Given the importance of PRMT and EGFR in colorectal cancer development and progression, investigators tried to further investigate the relation between EGFR and PRMT in colorectal cancer pathophysiology.