Malaria is caused by Plasmodium species transmitted by Anopheles mosquitoes. Following a mosquito bite, Plasmodium sporozoites migrate from skin to liver, where extensive replication occurs, emerging later as merozoites that can infect red blood cells and cause symptoms of disease. As liver tissue-resident memory T cells (Trm) have recently been shown to control liver-stage infections, we embarked on an mRNA-based vaccine strategy to induce liver Trm to prevent malaria. While a standard mRNA vaccine was unable to generate liver Trm, or protect against challenge with Plasmodium berghei sporozoites in mice, addition of an agonist that recruits T cell help from type I Natural Killer T cells under mRNA-vaccination conditions resulted in significant liver Trm generation and effective protection. Moreover, while prior exposure of mice to blood-stage infection impaired traditional vaccines based on attenuated sporozoites, mRNA vaccination was unaffected, underlining the potential for such a rational mRNA-based strategy in malaria-endemic regions.