Organ transplantation is the main treatment for organ failure. The functional protection of donor organs during ex vivo transportation is the key to the success of organ transplantation. How to protect the functions of donor organs during in vitro transportation is one of the key issues in the field of organ transplantation research. In a hypoxic environment, the 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 the 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 ischemia injury during cold storage. HIF-1α has been a hot spot in the research on the protective mechanism of cold ischemia injury of isolated organs. The intervention of the HIF-1α-related signal pathway is expected to become a new strategy for maintaining organ function during cold storage of isolated organs.