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Taking Ganoderma lucidum as the fermentation strain, the basal culture medium and Ginseng decoction mediums were screened.Meanwhile, the optimization of fermentation process of Ginseng decoction with G.lucidum strain and antifatigue activity of its fermentation product was studied in the paper.The results showed that the ingredients of optimum basal medium for the G.lucidum was glucose 5%, corn steep liquor 0.3%,soybean cake powder 1%, molasses 0.6%, MgSO4 0.075% and KH2PO4 0.15%.