Streptococcus suis serotype 2 is a Gram-positive bacterium that causes sepsis and meningitis in piglets and humans. The mechanisms of S. suis serotype 2 invasive disease are not well understood. The surface proteins of pathogens usually play important roles in infection and bacterium-host interactions. Here, we identified a novel surface protein that contributed significantly to the virulence of S. suis serotype 2 in a piglet infection model. This protein showed little similarity to other reported proteins and exhibited strong binding activity to human factor H (hFH). It was designated Fhb (factor H-binding protein). The fhb genes found in S. suis serotypes 1, 2, 4, 7, and 9 exhibited molecular polymorphism. Fhb possessed two proline-rich repeat sequences and XPZ domains, and one repeat sequence exhibited a high homology to Bac, an IgA-binding protein of Streptococcus agalactiae. Evidence strongly indicated that fhb-deficient mutants had diminished phagocytosis resistance in bactericidal assays. In addition, Fhb plays important roles in complement-mediated immunity by interacting with hFH. These findings indicated that Fhb is a crucial surface protein contributing to the virulence of S. suis, with important functions in evading innate immune defenses by interaction with host complement regulatory factor hFH.