High altitude environment is characterized by hypobaric hypoxia, low temperature and intense solar radiation. Among them, the most prominent one is hypoxia, and it can influence healthy individuals in many aspects. Acute high-altitude illness refers to acute mountain sickness (AMS), high-altitude cerebral edema (HACE) and high-altitude pulmonary edema (HAPE) which people may suffer from when ascending to an altitude level of over 2500 m. With more and more people having the demand into the plateau areas, the pathogenesis, prevention and treatment of acute high-altitude illness have received more attention. In present, the pathogenesis of the disease remains unclear, and thus little progress has been made in its pharmacologic prevention and treatment. In this article, we summarized the possible mechanisms of the illness in order to provide new targets for its prevention and treatment.