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Liver cancers contribute significantly to cancer-related mortality worldwide and liver transplants remain the cornerstone of curative treatment for select, early-stage patients. Unfortunately, because of a mismatch between demand and supply of donor organs, liver cancer patients must often wait extended periods of time prior to transplant. A variety of local therapies including surgical resection, transarterial chemoembolization, and thermal ablative methods exist in order to bridge to transplant. In recent years, a number of studies have examined the role of irreversible electroporation (IRE) as a non-thermal local ablative method for liver tumors, particularly for those adjacent to critical structures such as the vasculature, gall bladder, or bile duct. In addition to proving its utility as a local treatment modality, IRE has also demonstrated promise as a technique for donor organ decellularization in the context of whole-organ engineering. Through complete non-thermal removal of living cells, IRE allows for the creation of an acellular extra cellular matrix (ECM) scaffold that could theoretically be recellularized and implanted into a living host. Here, we comprehensively review studies investigating IRE, its role in liver cancer treatment, and its utility in whole organ engineering.