Salinity severely threatens land use capability and crop yields worldwide. Understanding the mechanisms that protect soybeans from salt stress will help in the development of salt-stress tolerant leguminous plants. Here we initially analyzed the changes in malondialdehyde levels, the activities of superoxide dismutase and peroxidases, chlorophyll content, and Na+/K+ ratios in leaves and roots from soybean seedlings treated with 200 mM NaCl at different time points. We found that the 200 mM NaCl treated for 12 h was optimal for undertaking a proteomic analysis on soybean seedlings. An iTRAQ-based proteomic approach was used to investigate the proteomes of soybean leaves and roots under salt treatment. These data are available via ProteomeXchange with the identifier PXD002851. In total, 278 and 440 proteins with significantly altered abundances were identified in leaves and roots of soybean, respectively. From these data, a total of 50 proteins were identified in the both tissues. These differentially expressed proteins (DEPs) were from 13 biological processes. Moreover, protein-protein interaction analysis revealed that proteins involved in metabolism, carbohydrate and energy metabolism, protein synthesis and redox homeostasis could be assigned to four high salt stress response networks. Furthermore, semi-quantitative RT-PCR analysis revealed that some of the proteins, such as a 14-3-3, MMK2, PP1, TRX-h, were also regulated by salt stress at the level of transcription. These results indicated that effective regulatory protein expression related to signaling, membrane and transport, stress defense and metabolism all played important roles in the short-term salt response of soybean seedlings.