The ability of bacteria to adapt to the external environment is fundamental for their survival. A halotolerant microorganism Enterococcus faecalis able to grow under high salt stress conditions was isolated in the present study. The SDS-PAGE analysis of the secretome showed a protein band with a molecular weight of 28kDa, gradually increased with an increase in salt concentration, and the highest intensity was observed at 15% salt stress condition. LC-MS/MS analysis of this particular band identified fourteen different proteins, out of which nine proteins were uncharacterized. Further, the function of uncharacterized proteins was predicted based on structure-function relationship using areverse template search approach deciphering uncharacterized protein into type III polyketide synthases, stress-induced protein-1, Eed-h3k79me3, ba42 protein, 3-methyladenine DNA glycosylase, Atxa protein, membrane-bound respiratory hydrogenase, type-i restriction-modification system methylation subunit and ManxA. STRING network analysis furthera showed strong association among the proteins. The processes predicted involvement of these proteins in signal transduction, ions transport, synthesis of the protective layer, cellular homeostasis and regulation of gene expression and different metabolic pathways. Thus, the fourteen proteins identified in the secretome play an essential role in maintaining cellular homeostasis in E. faecalis under high-salinity stress. This may represent a novel and previously unreported strategy by E. faecalis to maintain their normal growth and physiology under high salinity conditions.