Organ transplantation is the main treatment for organ failure. Functional protection of donor organs during ex vivo transportation is critical for the success of organ transplantation. How to protect the functions of donor organs during in vitro transportation is an important issue in the field of organ transplantation research. In a hypoxic environment, transcriptional activity of a series of genes in cells is activated. These genes are mainly involved in angiogenesis, iron metabolism, glucose metabolism, and cell proliferation/ survival. In aerobic organisms, hypoxia-inducible factor-1α (HIF-1α) is involved in the regulation of the expression of various genes to maintain homeostasis of tissues and cells under hypoxic conditions, thereby adapting to the hypoxia. Many studies have shown that the HIF-1α pathway plays an important role in protecting isolated organs from cold ischemic injury during cold storage. HIF-1α has been a hot topic in research on the protective mechanism of cold ischemic injury of isolated organs. Regulating the HIF-1α-related signaling pathway is expected to be a new strategy to maintain organ functions during cold storage of isolated organs.