Abstract:[Background] As a highly toxic heavy metal pollutant, the reduction of hexavalent chromium (Cr(VI)) by microbiological methods is not only economical but also environmentally friendly. [ObjectVIe] To explore the proteins or genes related the tolerance or reduction of Cr(VI) in chromium-resistant strain CM01, and to explain the tolerance mechanism of the strain at the molecular level. [Methods] The difference of protein expression in chromium-resistant strain CM01 under the Cr(VI) stress or not was analyzed by isobaric tags for relatVIe and absolute quantitation techniques (iTRAQ). The mRNA expression of 4 up-regulated proteins related to metabolic pathway was verified by RT-qPCR technique. The hydrophobicity of cell surface was determined by UV spectrophotometer. [Results] In this study, 2 570 proteins were identified and 646 were significantly different, of which 343 were up-regulated and 303 were down-regulated. Fe/Mn superoxide dismutase, betaine aldehyde dehydrogenase, pentose phosphate pathway, inositol phosphate pathway and amino acid metabolism in CM01 were involved in the response mechanism to exogenous Cr(VI). The results of RT-qPCR experiments showed that the gene transcription levels and protein level of the four proteins involved in metabolic pathways were consistent. The cell surface hydrophobicity of CM01 in the control group was higher than that in the experimental group. [Conclusion] Cr(VI) response mechanism of chromium-resistant bacteria was preliminarily explored in this study, which provides theoretical support and new research ideas for the use of microorganisms to control environmental pollution.