The main aim of this study was to demonstrate that the surface immunogenic protein (Sip) of the aquatic pathogen Streptococcus agalactiae is a potential candidate for vaccine development for Oreochromis niloticus. In this study, a Sip was identified. Alignment analysis indicated that the Sip protein was highly homologous with Sip proteins from other S. agalactiae isolated from humans (99%). SDS-PAGE procedure indicated that the Sip protein was successfully expressed in Escherichia coli BL21 (DE3). The recombinant Sip protein was purified by affinity chromatography, and the mouse anti-Sip serum was produced. Tilapia Oreochromis niloticus were vaccinated with Sip, and immunogenicity was confirmed by subsequent western blotting. Enzyme-linked immunosorbent assay (ELISA) analysis demonstrated that Sip produced an observable antibody response in all sera of the vaccinated fish. The relative percentage survival (RPS) value for the Sip vaccine was 90.62. Tilapia vaccinated with Sip produced specific antibodies, and were highly resistant to infection by the virulent S. agalactiae. These results indicate that Sip is an effective vaccine candidate against S. agalactiae for tilapia, Oreochromisniloticus.