Increasing knowledge of the immunosuppressive tumor microenvironment in cancer-related processes has led to the developing of novel immune-based therapies that have changed the cancer treatment paradigm. In the tumor microenvironment, the plethora of soluble factors secreted by tumor cells interacts with immune cells and non-immune components to deliver signals necessary for tumor progression. Accordingly, targeting tumor-derived factors inducing this immunosuppressive tumor microenvironment has become an appealing therapeutic potential in advancing cancer treatment. CCL20, a chemokine best known to induce leucocyte migration in response to pathological and inflammatory conditions, has been implicated in tumor proliferation, angiogenesis, metastasis, immunosuppression, and therapeutic resistance. Notably, CCL20 and its receptor CCR6 are important in tumor microenvironment interactions. This review discusses the interaction between the CCL20-CCR6 axis and the tumor microenvironment and how these interactions promote tumor progression. Also, an outline of studies utilizing CCL20 in combination with other standard cancer treatments has been shed.