[Abstract] Background Ischemia–reperfusion–induced lung injury is characterized by non- specific alveolar damage, lung edema, and hypoxemia after lung transplantation，Ultimately cause delayed graft function and primary grft dysfunction. Objective The process of gene silencing may be exploited by the use of small interfering RNA (siRNA) to mediate precise control of targeted cellular functions，which could provide a new strategy to ameliorate lung IRI. Content This review will provide an overview of current concepts in RNAi and the target therapy to other organ IRI,and application in lung IRI. Trend The therapeutics based on RNAi is a new and promising strategy,which apply in ameliorating IRI of organ transplantation become more and more mature, thus allow current RNAi trials in lung transplant will bring RNAi therapy to clinical reality in the future.