Ganoderma lucidum is commonly known as medically potent mushroom, which has been widely used in China and other oriental countries for the treatment of various diseases, including cancer. In this report, we investigated the anti-oxidant and protective effect of Ganodema lucidum extract (GLE) against the DNA damage induced by free radical and U.V. In the assay of cell growth inhibition, the inhibitory cell growth rate induced by hydroxyl radical was dose-dependently decreased by GLE. This results support that GLE has a detoxifying activity against cytotoxicity of hydroxyl radical in E. coli cell. GLE also protected ColE1 plasmid DNA damage in the concentration of 200$mu extrm{g}$ per reaction on the DNA fragmentation assay. The nuclear tailing by hydrogen peroxide in single cell gel electrophoresis(SCGE) was decreased by GLE in the concentration of 50$mu extrm{g}$/ml. These data indicate that Ganoderma lucidum has an anti-oxidative activity to hydrogen peroxide. The mutation rate after irradiation of U.V. was reduced by 50$mu extrm{g}$/ml GLE and total number of Rif (Rifampicin) resistant mutants was decreased in a concentration dependent manner when added the GLE exogenously in a culture media. According to the results, it is likely that GLE has not only an anti-oxidative activity to hydroxyl radical but also an anti-mutagenic activity to U.V. mutagenesis.