Abstract: Solanum nigrum is a typical heavy metal-hyper-accumulator. However, the molecular mechanisms underlying the tolerance and accumulation of heavy metal have remained largely unclear. To through light on the mechanism of Cd accumulation in Cd hyper-accumulator S. nigrum, we investigated the response of S. nigrum to Cd toxicity at root and leaf proteomic levels using 2-DGE technique. The root and leaf 2-DGE maps, respectively, consisted of at least 927 and 1 025 reproducible protein spots, of which 45 and 57 were classified as differentially expressed proteins. Through MALDI-TOF MS analysis, 9 and 12 of the spots identified, representing 9 and 6 proteins in root and leaf, respectively. The proteins were involved in phytohormone synthesis, defense responses, and energy metabolism and construction. This showed that proteomic analysis explained Cd response mechanisms in hyper-accumulator S. nigrum. It also provided theoretical basis for phytoremediation of heavy metal-contaminated soils through modern biotechnology.