Mercury is considered to be "a global pollutant" and raises concern worldwide. Once mercury enters the body, it will be distributed all over the body but will accumulate in the brain, kidney and liver. To date, no substance originating from edible fungi capable of adsorbing mercury has been reported. We found that the mushroom Grifola frondosa exhibited mercury adsorption capacity. A polysaccharide-peptide (GFPP), displaying the unique N-terminal amino acid sequence of APPGMHQKQQ and 7 partial sequences with high reliability obtained by LC-MS/MS, was isolated by hot-water extraction of its fruiting bodies followed by ion exchange chromatography and gel filtration chromatography. Two rat models were employed to determine the dose and the duration of HgCl2 treatment (given by acute administration or continuous treatment) to test if G. frondosa could promote mercury elimination. For rats subjected to acute treatment with HgCl2, both GFPP and G. frondosa fruiting bodies (GFFF) could accelerate the decline of blood mercury level, which fell precipitously by 50% on the second day. GFPP and GFFF also promoted elimination of the burden of mercury in the liver and kidneys. For rats receiving continuous HgCl2 treatment, G. frondosa prevented the progressive increase of blood mercury level, and kept the blood mercury level within a relatively stable range.