The invention discloses a long-acting artesunate drug for preventing schistosome infection and a preparation method thereof. According to the method, a low immunogenicity GST-NSP protein is adopted, a chemical coupling method is employed to couple artesunate (AS) having an effect with the GST-NSP protein so as to prepare an (AS) n-GST-NSP conjugate. While maintaining the adolescent schistosome killing activity of the AS, the conjugate prolongs the half-life period of the AS in a host, not only has an early treatment effect on schistosome infection, and also has a function of preventing schistosome infection, thus providing a new means for preventing schistosome infection of human and a variety of reservoir animal hosts, and controlling the epidemics of schistosomiasis. The drug provided in the invention has good application prospects the pharmacy field, including treatment and prevention of schistosomiasis.