Helicobacter pylori produces a novel nucleomodulin, tumour necrosis factor (TNF)-a-inducing protein (Tipa), which was reported to bind eukaryotic DNA, upregulate TNF expression and promote carcinogenesis. Tipa is secreted in a soluble form by the bacterium, but how it enters host cells and traffics to the nucleus was not clear. As Tipa was identified in the proteome of H. pylori extracellular vesicles (EVs), we hypothesised that these membrane “blebs” may mediate the secretion and delivery of Tipa to the nucleus, resulting in perturbed nuclear processes that promote carcinogenesis. To address this, H. pylori tipA and tipA/tipA+ mutant strains were generated and their EVs characterised by Western blotting, Nanoparticle Tracking Analysis and electron microscopy. We confirmed that H. pylori EVs harbour Tipa. We also identified strain-specific differences in the amounts of Tipa secreted by the bacteria, but contrary to a previous report, there was no correlation between the amounts secreted and disease outcome. Importantly, we demonstrated that most of the Tipa in culture supernatants was associated with EVs, suggesting that this is the main secretion mechanism for the protein. Following co-incubation of EVs with AGS epithelial cells, we could detect Tipa in the nuclear compartment at 4-hours post-incubation. Consistent with previous work, recombinant Tipa induced TNF production in THP-1 cells. Conversely, EVs lacking Tipa induced significantly more TNF (p = <0.0001) and interleukin-8 (IL-8; p = 0.0439) than WT or tipA/tipA+ EVs. In AGS cells, tipA EVs also induced significantly more IL-8 than those from WT EVs (p = 0.0129). These data show that soluble and EV-associated Tipa may have different biological effects on host cells. In conclusion, we propose that EVs are the major mechanism for the secretion and delivery of Tipa to the nucleus, thereby modulating host immune responses and promoting gastric carcinogenesis.