Fusobacterium nucleatum is a Gram-negative anaerobic bacterium prevalent in the human oral cavity. This oral commensal bacterium has been shown as the main contributor for many dental diseases, including periodontitis and gingivitis. Recently, evidence has verifying the linkage between F. nucleatum and carcinogenesis of colorectal cancer (CRC). Outer membrane vesicles (OMVs) are naturally occurring metabolic byproducts secreted by Gram-negative bacteria, and contain highly antigenic LPS and outer membrane protein residues. Due to its antigen containing and non-self-replicated properties, OMVs are emerging as a powerful platform for vaccine design and delivery. We speculated the OMVs from F. nucleatum might contain antigens able to elicit effective immune response. In this study, we identified 98 proteins from purified OMVs of F. nucleatum through proteomic studies. In silica analysis indicates the non-replicative OMVs of F. nucleatum contain a variety of antigenic virulence factors and may play a critical role in vaccine design.