The present invention discloses a sterilization composition adopting fluxapyroxad and picoxystrobin as main active components, and an application thereof, and belongs to the technical field of compounded pesticides. According to the present invention, the sterilization composition adopts fluxapyroxad and picoxystrobin as main active components, wherein a weight ratio of the fluxapyroxad to the picoxystrobin is 1-90:1-90, and the total amount of the fluxapyroxad and the picoxystrobin is 2-90% of the mass of the sterilization composition; and the sterilization composition provides significant effects for preparation of drugs for prevention and control of crop resistance plant fungous diseases of cereals, fruits and vegetables, and specifically for preparation of sterilization drugs for prevention and control of powdery mildew, botrytis cinerea, sclerotinia rot, rot disease, rust disease, glume spot of rice, web blotch, downy mildew, rice blast and seedling blight, especially sterilization drugs for prevention and control of rice blast and cucumber powdery mildew. In addition, compared with the single-agent substance, the composition has characteristics of prevention and control spectrum expanding, production and use cost reducing, and drug resistance overcome and delaying.