Infection with the Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) results in a chronic and occasionally severe illness that affects pregnant sows and is characterized by respiratory issues, weight loss, poor growth performance, and reproductive failure. The emerged messenger RNA (mRNA) is a promising approach to preventing various diseases due to its favorable safety profile, ease of design, and scalable production. In this study, we developed a messenger RNA (mRNA) vaccine against a highly pathogenic PRRSV strain HuN4. Recombined multiple antigenic proteins, including GP5-M, GP3-NSP9, and GP2-GP4, were designed and codon-optimized. Indirect immunofluorescence assay (IFA) and Western blot detected the expression levels of different mRNA-LNPs. The outcomes of IFA demonstrated that GP3-NSP9 and GP2-GP4 had stronger fluorescence in their mRNA-LNP expressions, GP3-NSP9 expressing themselves better than GP2-GP4. Conversely, GP5-M exhibited hardly little fluorescence. The GP2-GP4 and GP3-NSP9 fusion proteins were expressed in the cells, according to the Western blot data. However, GP5-M was not. The GP3-NSP9 and GP2-GP4 were used to immunize pigs alone or in combination. The challenge of PRRSV HuN4 after immunization revealed that N protein antibody titers and viral load in the blood and lungs were much lower than those of mock-challenged pigs. All piglets were euthanized, and their lungs were examined macroscopically and histopathologically. In addition, the GP2-GP4 and GP3-NSP9 combined mRNA immunization showed effective and protective immune response than GP3-NSP9 mRNA individual immunization.