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<i>Salmonella enterica</i> serovar Enteritidis (<i>S</i>. Enteritidis) is an important zoonotic pathogen that can lead to diarrhea and systemic infections in humans and mortality in animals. This is a major public health issue worldwide. Safe and effective vaccines are urgently needed to control and prevent <i>Salmonella</i> infection. Subunit vaccines are safe and provide targeted protection against <i>Salmonella</i> spp. Here, we developed and evaluated an <i>S</i>. Enteritidis subunit vaccine candidate, the rHis-SseB adjuvant with simvastatin. We amplified the <i>SseB</i> gene from <i>S</i>. Enteritidis C50041 genomic DNA and expressed the recombinant proteins rHis-SseB and rGST-SseB using the <i>Escherichia coli</i> system. Western blotting confirmed the immunoreactivity of recombinant proteins rHis-SseB and rGST-SseB with antisera against <i>Salmonella</i> Enteritidis C50041. In a mouse model of intramuscular vaccination, co-immunization with rHis-SseB and simvastatin significantly enhanced both the SseB-specific antibody titer in serum (humoral immune response) and splenic lymphocyte proliferation (cellular immune response). Co-immunization with rHis-SseB and simvastatin provided 60% protection against subsequent challenge with the <i>S</i>. Enteritidis C50041 strain and decreased bacterial colonization in the liver and spleen. These findings provide a basis for the development of an <i>S</i>. Enteritidis subunit vaccine.