In our previous works, strain CZ130302, as a representative of the new serotype Chz of Streptococcus suis, has a high potential to be virulent and associated with meningitis in animals. However, the pathogenic mechanism of the serotype Chz SS is not known. In this study, we sequenced and annotated the genomes of strain CZ130302 and two avirulent strains (HN136 and AH681). The results of comparative genomics showed that two avirulent strains HN136 and AH681 were much closer to each other and two unique 50 K and 58 K genomic islands were revealed in strain CZ130302. To investigate the functions of the two islands, mutant strains (Δ50K-CZ130302 and Δ58K-CZ130302) were constructed, and then both islands, especially the 50K island, were confirmed to attenuate the virulence of S. suis CZ130302 in BALB/c mice. In addition, a set of SecY2/A2 secretion system and the effector protein, named Streptococcus suis Serine-rich Repeat Protein 1(SssP1), were demonstrated to fulfill critical roles in pathogenicity, which was an essential component of the 50K island. Furthermore, two recombinant proteins containing two Ig-like fold subdomains of SssP1 respectively were identified to have the ability to bind HBMEC cells by the indirect immunofluorescent assay. Meanwhile, strain ΔSssP1 showed a significant reduction both in HEp-2 and HBMEC cells compared with wild-type strain. Both the transmission electron microscope and immunofluorescence assays showed that the SssP1 can form fimbriae-like structures extending outwardly from the bacterial surface.