ABSTRACT: Growing evidence indicates the potential of developing novel polysaccharide-based adjuvant for tumor therapy from edible mushrooms, including Ganoderma lucidum. In the present study, a novel polysaccharide preparation (GLPP) was isolated from the fruiting body of G. lucidum grown in Anhui, China, and characterized for its physicochemical properties. GLPP had an average molecular weight of 6600 and a specific optical rotation of +25.6°, contained 10.6% protein, and had a molar ratio of 0.9:15:1 for mannose, glucose, and galactose, respectively. GLPP was also investigated and compared with PSP (polysaccharopeptide preparation), a commercial antitumor and immunostimulating agent, for its antitumor and immunostimulation capacity, and potential in reducing the toxic effects induced by cyclophosphamide (Cy) treatment and Cobalt-60 (60Co) radiation in mice. GLPP at levels of 100 and 300 mg/kg body weight (BW)/d significantly inhibited the growth of inoculated S180, Heps, and EAC tumor cells in mice. GLPP at a dose of 300 mg/kg BW/d showed stronger growth inhibition against all 3 tested tumor cells than PSP at 1 g/kg BW/d. GLPP also dose-dependently increased phagocytic index, phagocytic coefficient, and 50% hemolysin value in the EAC tumor-bearing mice, indicating its potential immunostimulating property. In addition, GLPP at 300 mg/kg BW/d was comparable to PSP at 1000 mg/kg BW/d in preventing the decrease of thymus index, spleen index, white blood cells, and bone marrow karyote numbers induced by Cy treatment and 60Co radiation. These data demonstrated the potential utilization of GLPP as an adjuvant to conventional treatments of cancers and its use for cancer prevention.