Objective To raise the destruxin A production of Metarhizium anisopliae by optimizing culture conditions of liquid fermentation.Method Experiments were designed by response surface methodology (RSM). The key factors affecting the liquid fermentation were screened by Plackett-Burman design and central composite design.Result A model with high fitting degree and small error was obtained. The optimum culture condition of this model was 22.7 g·L^-1 sucrose, 13.4 g·L^-1 peptone and 9.70 d for fermentation. The maximum predicted concentration of destruxin A was 6.90 μg·mL^-1, while the actual measured concentration was 6.89 μg·mL^-1.Conclusion The results can provide a theoretical basis for large-scale fermentation of M. anisopliae and production of crude toxin, which can potentially enable the widespread development and application of crude toxin.