Abstract: The effect of extracellular acidosis on proteome of immature dendritic cells（imDCs） was investigated in this study, so as to lay a preliminary foundation for further study on the molecular mechanism of imDCs function regulated by acidic pathological microenvironment. Mouse bone marrow cells were induced to differentiate into imDCs, then the proteome of imDCs was investigated using Label-free quantification after treatment with pH6.5 for 24 h. The result revealed that expression of 389 proteins changed significantly after pH6.5 treatment. GO was used to analyze the cell composition, molecular function and biological processes involved in differentially expressed proteins, and KEGG was used to analyze the relevant signal pathways involved in differentially expressed proteins. The results revealed that differentially expressed proteins were involved in ribosomes, ion transmembrane transport, cellular respiratory regulation, Huntington′s disease signaling pathway, nucleotide-binding oligomerization domain（NOD） like receptor signaling pathway and cyclic adenosine monophosphatec（cAMP） signaling pathway, etc. The interaction network of differentially expressed proteins was presented by Cytoscape software, and then key proteins were selected according to the number of nodes. The results showed that the key differentially expressed proteins, including ribosomal protein S27 A, S23, L21 and CREB-binding protein（CREBBP）, were down-regulated, amyloid precursor protein（APP） and soluble N-ethylmaleimide-sensitive factor attachment protein receptors homolog（YKT6） were up-regulated.