Lon protease is the first identified ATP-dependent protease that plays critical role in degrading misfolded proteins and maintaining intracellular protein balance in prokaryotes. Recent studies have suggested that, as a pressure-stress protein, Lon was involved in the degradation of a variety of transcription regulators and two-component regulatory system in bacteria, resulting in altered physiologically metabolic process of bacteria cells to adapt to the environment change. In this paper, the structure, function, and up and down-stream regulatory network of bacterial Lon protease are reviewed, aiming at enhancing understanding in the physiological function of Lon, as well as providing basis for elucidating the mechanism of intracellular regulation.