Hypoxia is an important part of the pathogenesis of many chronic respiratory and cardiovascular diseases, cerebral ischemia, and solid tumors, and other major diseases. Cell hypoxia models provide an important tool for analyzing the mechanism of hypoxia responses and for screening potential therapeutic targets. The scientific aspects and applicability of model construction, however, can directly affect the reliability of the research conclusion ,and are thus of great significance to the development of related disease prevention and treatment research. Research on the construction and application of cell hypoxia models has currently achieved stage-by-stage result , but there are still some limitations in terms of the model-evaluation system and tissue cell specificity. This paper summarizes the current status of research on the mechanism of hypoxia occurrence and development and the evaluation of indicators. We combine the tissue-specific characteristics, and discuss the construction and optimization of the cellular hypoxia model to provide a reference for future model construction and to support future research, development, and translation of targeted therapies.