Non-melanoma skin cancers are a common reality worldwide. The principal cause that determines the occurrence of these diseases is the exposition of the sun, which principally causes an alteration in the immune system. Therefore, it is possible that other forms of innate or acquired alterations of the immune system could favor the occurrence of non-melanoma skin cancers. For example, several studies have demonstrated that immunosenescence creates an immunosuppressive state that encourages the development of malignances, and new discoveries have noted the importance of T cells and in particular of T regulatory cells (Treg) and T receptor CD28 in this mechanism. Similar results are obtained analyzing the effect of immunosuppressive drugs. The importance of the immune system and its alteration in the genesis of non-melanoma skin cancers is fundamental for the creation of a new therapeutic and less invasive approach.