HMGB1 is an important therapeutic target and prognostic predictor of ischemic stroke and hemorrhagic transformation; however, based on the complex biphasic role of HMGB1 and the variability in treatment times between clinical and experimental models, the efficiency and safety of targeting HMGB1 in the acute treatment of cerebral infarction and long-term rehabilitation remain a major challenge in this clinical area at present. The gene discussed is HMGB1; the disease is cerebral infarction.