Abstract: The tolerance of microorganism under acid stress is of significant importance to the growth and industrial production of bacterial strain. When the bacterial cells are exposed to the external acid environment, proteins in periplasmic space are under higher acid stress and are thusmore susceptible to severe damage from acid than the intracellular protein, and these are also more susceptible to severe damage from acid than the intracellular protein. During the acid-resisting process of Gram-negative bacteria, in addition to the intracellular decarboxylase system, the molecular chaperone can also participate in the identification and protection of the space structure of protein as an important "correcting" mechanism. This paper, reviews the current researches on the function, structure, acid-resisting mechanism of variousmolecular chaperones, including HdeA, HdeB, DnaK and GroEL. Finally, the research progress of the acid-resisting mechanism among Gram-negative bacteria is summarized. Through in-depth investigation and analysis of the physiological adaptation strategy of molecular chaperone to the acid stress environment, this study can help to conduct physiological property modification of target strain and improve their viability and tolerance in acid stress environment, which has its important theoretical and practical significance.