Abstract: In this paper,the optimal conditions for the fermentation of Grifola frondosa were studied by response surface methodology with glucose,peptone,KH₂PO₄,fruit and vegetable jujce dosage as factors and mycelia biomass as the index,and the antioxidant activity of mycelia was measured. The results showed that the optimal formula was:glucose dosage 2.5%(w·v^-1),peptone dosage 0.5%(w·v^-1),KH₂PO₄ dosage 0.1%(w·v^-1),fruit and vegetable juice dosage 15%(v·v^-1). In this condition,the mycelial dry weight prediction value was 19.06 mg·ml^-1,and the actual measured value is(18.12±0.214) mg·mL^-1 within the error range. The results showed that the scavenging rate of DPPH radical was 69.78%±6.17% when the mass concentration was 1.5 mg·mL^-1,and the clearance rate of ABTS free radical was 82.11%±7.24%;Hydroxide radical scavenging rate reached 59.73%±3.15%. Thus,the mycelia of the submerged fermentation of Grifola frondosa could be used as a potential antioxidant.