The reactionary and reparative dentin formed by surviving odontoblasts and newly differentiated odontoblast-like cells protect the pulp from further damage. Our previous study has indicated that stem cells exist in carious pulp and are named carious dental pulp stem cells. CDPSCs displayed an increased proliferative capacity and enhanced alkaline phosphatase activity, mineralization ability, and the expression of osteogenesis/dentinogenesis-related genes compared with DPSCs. Though the biological characteristics of these two stem cells have been well analyzed, the molecular mechanisms responsible for the biological differences between CDPSCs and DPSCs are still unclear. Mass spectroscopy based proteomics is becoming an efficient method characterized by systematic large-scale qualitative and quantitative mapping of the whole proteome of stem cell phenotypes from different niches, allowing for the rapid understanding the mechanisms that control their self-renewal ability, differentiation potential and regeneration capacity. Previous studies compared the protein expression profiles in mesenchymal stem cells derived from human periodontal ligament, dental pulp, dental follicle, and dental papilla to provide a database for proteins commonly or differentially expressed among various dental stem cell populations,. Recently analyzed the proteomic profiling of SHED to reveal the abundantly expressed proteins. In this work, we performed two-dimensional fluorescence difference gel electrophoresis in combination with matrix-assisted laser desorption ionization time-of-flight mass spectrometry to identify the differentially expressed proteins between DPSCs and CDPSCs and to explore the candidate molecular markers contributing to the regeneration of dental structures in stem cell-based tissue engineering protocols. Recent studies have reported that DPSCs are able to differentiate into various cell types or tissues including osteoblasts, odontoblasts, chondroblasts,, adipocytes, neuronal cells, endothelial cells, melanocytes and cornea. Among these, the most important function of DPSCs is forming odontoblasts, however; the mechanisms that are responsible for DPSCs migration, proliferation, and differentiation when the tooth encounters deep caries are poorly known. Our study revealed that both DPSCs and CDPSCs had fibroblast-like morphology and were shown to be capable of differentiating into various cell types including osteoblasts, adipocytes and chondrocytes. Moreover, CDPSCs had a higher proliferative potential than DPSCs, which was consistent with the previous study. To better understand the molecular mechanisms underlying the changes in DPSCs encountering deep caries, we used 2D-DIGE to identify the proteins differentially expressed between DPSCs and CDPSCs. The comparative narrow range PH analysis showed that most differentially expressed proteins such as carious lesion, attrition and abrasion.