Abstract: Objective: To investigate the mechanism of acid resistance induced by repeated stress treatment with citric acid for Salmonella typhimurium CGMCC 1.1190. Methods: The acid-resistant strain of CGMCC 1.1190 was obtained after stress treatment in TSB liquid medium adjusted to pH2.5 by citric acid and transferred and incubated 12 times. The proteome of the acid-resistant strain of CGMCC 1.1190 was analyzed based on iTRAQ technology, with clustering analysis of the differential proteins by GO functional annotation and enrichment for biological processes, molecular functions, and cellular components, and KEGG annotation and enrichment for combined analysis of the pathways involved in the differential proteins. Results: The iTRAQ results showed that the CGMCC 1.1190 acid-resistant strain had 2373 proteins, of which 195 differential proteins, including 95 significantly down-regulated proteins and 100 significantly up-regulated proteins. GO analysis and KEGG analysis showed that CGMCC 1.1190 acid-resistant strains highly express stress protein-related genes, which could contribute CGMCC 1.1190 to enhance acid resistance by synthesizing some proteins in response to external stimulation. The high express cell membrane-related proteins could increase the integrity of CGMCC 1.1190 cell membrane, and the high expression of flagellar-related proteins could enhance the motility and increase the formation of protective biofilm of CGMCC 1.1190. The high expression of two-component system-related proteins could enhance acid resistance of CGMCC 1.1190 by regulating the production of acid kinins. The low expression of ABC transport system-related proteins could reduce the permeability of the cell membrane to H⁺ to protect the bacterium, and the proteins related to the energy metabolism pathway were highly expressed to provide energy and maintain the homeostasis of the CGMCC 1.1190 bacterium in response to acid stress. Conclusion: CGMCC 1.1190 could initiate a series of response mechanisms and survive after citric acid stress at pH2.5 due to some changes in protein expression.