Chemokine receptor CCR6 is expressed on various cells such as B cells, immature dendritic cells, innate lymphoid cells (ILCs), regulatory CD4 T cells, and Th17 cells. CCL20 is the only known high-affinity ligand that binds to CCR6 and drives CCR6 cells' migration in tissues. CCL20 is mainly produced by epithelial cells, and its expression is increased by several folds under inflammatory conditions. Genome-wide association studies (GWAS) in patients with inflammatory bowel disease (IBD), psoriasis (PS), rheumatoid arthritis (RA), and multiple sclerosis (MS) showed a very strong correlation between the expression of CCR6 and disease severity. It has been shown that disruption of CCR6-CCL20 interaction by using antibodies or antagonists prevents the migration of CCR6 expressing immune cells at the site of inflammation and reduces the severity of the disease. This review discussed the importance of the CCR6-CCL20 axis in IBD, PS, RA, and MS, and recent advances in targeting the CCR6-CCL20 in controlling these autoimmune diseases.