Background: Korean ginseng (Panax ginseng Meyer) has long been cultivated as an important medicinal plant. Moderate water loss resulting form drought stress can impairs the growth of ginseng and lead to yield reduction. However, the mechanisms by which drought stress affects ginseng at the proteome level remain pooly undersood.<BR>Methods and Results: We carried out label-free quantitative proteomic analysis of ginseng roots subjected to drought stress (grown at less than 10% soil moisture for 2 weeks) and, compared the results with a control samples of ginseng grown at 25% soil moisture. The analysis was carried out using liquid chromatography with tandem mass spectrometry. A total of 2,471 proteins were identified, and 195 of which showed significant modulation. Functional classification revealed that proteins involved in calcium signaling, and photosynthesis and, production of secondary metabolites were enriched in the control sample (cluster_1), whereas proteins associated with stress response redox reaction, electron transport, and protein synthesis were enriched in the drought-stressed root (cluster_2).<BR>Conclusions: Our results provide an overview of drought-induced proteomic changes in ginseng root, and illuminate their correlation with physiological changes, revealing potential proteomic markers of drought stress in ginseng.