Irreversible electroporation (IRE) with microsecond-pulsed electric fields (μsPEFs) can effectively ablate hepatocellular carcinomas in animal models. This preclinical study evaluates the feasibility and safety of IRE on porcine livers. Altogether, 10 pigs were included. Computed tomography (CT) was used to guide two-needle electrodes that were inserted near the hilus hepatis and gall bladder. Animals were followed-up at 2 hours and at 2, 7 and 14 days post-treatment. During and after μsPEF ablation, electrocardiographs found no cardiovascular events, and contrast CT found no portal vein thrombosis. There was necrosis in the ablation zone. Mild cystic oedema around the gall bladder was found 2 hours post-treatment. Pathological studies showed extensive cell death. There was no large vessel damage, but there was mild endothelial damage in some small vessels. Follow-up liver function tests and routine blood tests showed immediate liver function damage and recovery from the damage, which correlated to the pathological changes. These results indicate that μsPEF ablation affects liver tissue and is less effective in vessels, which enable μsPEFs to ablate central tumour lesions close to the hilus hepatis and near large vessels and bile ducts, removing some of the limitations and contraindications of conventional thermal ablation.