Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen responsible for various swine diseases and human cases of streptococcal toxic shock syndrome. RNA-binding protein RbpA can modulate gene expression through post-transcriptional regulation. Macrophages are one of the host immune cells and play an important role in resisting the invasion of pathogens such as bacteria. The potential targets of RbpA were analyzed by comparing the proteome of rbpA gene deletion strain (△rbpA) and parent strain (ZY05719). In addition, raw macrophages were used to incubate the parent bacteria to obtain the treatment group (macrophages treated ZY05719, recorded as macrophages group). The proteomic differences between the treatment group and ZY05719 group were compared to analyze the potential mechanism of Streptococcus suis against macrophage killing.