Salinity is one of the most important abiotic environmental factors for marine animals. If salinity deviate from optimum, adaptive mechanisms switch on to maintain organism’s physiological activity. In this study the proteome of the marine snails Littorina saxatilis from natural habitats (12, 23 and 32‰ and in response to experimental salinity decreasing (from 20‰ to 10‰) was analyzed. The isolation of all snails inside their shells and gradually declining mortality was observed under an acute experimental salinity decrease. Proteomic changes were evaluated in the survived experimental molluscs compared to control individuals using differential 2D gel-electrophoresis (DIGE) and subsequent LC-MS/MS-identification of proteins. Approximately 10% of analyzed proteins underwent up- or down regulation during the experiment. Proteins of folding, antioxidant response, intercellular matrix, and metabolic enzymes were identified among them. Proteomic changes observed in experimental hypoosmotic stress partially reprodu