During liver cancer progression, the body's regional immune response is the major force that remodels the tumor microenvironment. However, the inflammatory response resulting from inevitable ischemia and reperfusion injury may induce an immune-suppressive environment that favors tumor recurrence after liver transplantation. A comprehensive review in this special issue, "Immunology," summarizes the most recent evidence contributing to a complete picture of intrahepatic inflammatory and immune regulation for cancer recurrence after liver transplantation. The intrahepatic humoral microenvironment features an exacerbated inflammatory response promoting tumor growth, angiogenesis, invasiveness, and metastasis. In addition, the cellular microenvironment in the liver is characterized by the mobilization of regulatory immune cells that promote the escape of tumor cells from immune surveillance and elimination. This up-to-date depiction of regional immune regulation indicates potential immunologic biomarkers for post-transplant cancer recurrence, along with promising new immunotherapy.