The invention relates to a nontoxic clostridium perfringens and clostridium septicum fusion protein vaccine and a production method thereof. The fusion protein vaccine prepared by the method adopts aclostridium perfringens epsilon toxin which is subjected to codon optimization and contains three amino acid mutations, and spoilage which contains four amino acid mutations and eleven amino acid deletions, namely not only kept the integrity and spatial conformation of the natural toxin are to the maximum extent, but also the biological safety hazard caused by single amino acid mutation is avoided. The vaccine also has the advantages of simple preparation process, excellent vaccine efficacy and the like, greatly reduces the biological safety risk in the vaccine production process. Compared with the current commercialized sheep fast-epidemic and sheep enterotoxemia inactivated vaccines in China, the vaccine is an ideal candidate vaccine for upgrading existing clostridium perfringens and clostridium septicum vaccines in China; in addition, when combined vaccines are prepared by the vaccine together with other antigens, the combined vaccine can be prepared without increasing the use doseof the combined vaccine.