ObjectiveTo investigate the working principles, recent advances, and combined therapeutic efficacy of irreversible electroporation (IRE) in pancreatic cancer treatment when integrated with conventional therapies (e.g., surgery, chemotherapy, radiotherapy, immunotherapy), and to evaluate its potential for improving patient survival outcomes and quality of life. MethodsA comprehensive analysis of recent IRE researches in pancreatic cancer was performed, elucidating therapeutic mechanisms, technical merits, clinical limitations, and combinatorial effects with conventional therapies through examination of clinical trials and prospective studies. ResultsIRE induces irreversible nanopores in tumor cell membranes via high-intensity electric fields, disrupting membrane integrity and triggering apoptotic cell death. Notably, it promotes immunogenic cell death, activating dendritic cells and initiating tumor-specific immune responses. When combined with surgery, chemotherapy, radiotherapy, or immunotherapy, IRE enhances therapeutic efficacy, prolongs survival in locally advanced pancreatic cancer patients, reduces postoperative recurrence rates, and significantly improves quality of life. ConclusionsAs a non-thermal ablation technique, IRE demonstrates unique advantages in localized pancreatic cancer treatment, particularly for surgically ineligible patients, and serves as a potent adjunct to traditional therapies. With technological refinements and accumulating clinical evidence, IRE is poised to play an increasingly pivotal role in future oncology practice.