Major Histocompatibility Complex (MHC) is a gene region, which is named human leucocyte antigen (HLA) in humans. The human leukocyte antigen (HLA) system is a highly polymorphic family of genes involved in immunity and responsible for identifying self-cells versus no self-cells. Although HLA typing is essential for solid organ and bone marrow transplantation, at present, MHC is going to study on cancer immunotherapy increasingly. In order to introduce MHC related to cancer immunotherapy, the chapter aims at focusing on several MHC issues related to cancer immunotherapy. For example, MHC research and development (R&D) in MHC class I molecular loss related to cancer immunotherapy; tumor immune escape related to nonclassical MHC I; T-cell epitope vaccines; as well as MHC issues in adoptive immune cell therapy and personalized immunotherapy. In each part for MHC related to immune responses for tumor disease, we also introduce clinical uses in a study on MHC issues for T-cell immunotherapy, MHC for T-cell vaccines, and MHC TCR reconstructions for tumor shared/specific antigen related TCR T-cell personalized immunotherapy.