Objective: To study the wine-processed techniques of venenum bufonis and screen out the optimum processing technique. Method : The orthogonal test was applied to study the wine-processed techniques. HPLC fingerprint was used to determine the total retention rate of cinobufagin and resibufogenin. Result : Relative importance of factors affecting wine-processed techniques were as follow: processing time > processing temperature> ratio of botanical and auxiliary materials. The processing time had a remarkable effect. Chemical compositions decreased after venenum bufonis was processed by wine. The optimum processing technique was that venenum bufonis was processed at 60 ℃ by 55% ethanol and ratio of 1 ∶2 for 12 h. Conclusion : The method is steady with a simple operation and can provide a basis to set up a standardized wine-processed technique of venenum bufonis.