Therapeutic tumor vaccines hold great promise for effective tumor immunotherapy, however orally administered tumor vaccines that can stimulate a robust immune response are still limited. The major challenges in oral vaccines are the complex gastrointestinal environment and intestinal epithelial barriers. Numerous intestinal commensal bacteria interact with the host immune cells through the release of outer membrane vesicles (OMVs) which can penetrate the intestinal epithelial barriers. Here, we present an effective tumor vaccine based on the OMVs which are generated by orally administered genetically engineered bacteria in intestine. A tumor antigen was fused with the surface protein ClyA on OMVs, whose expression was controlled by an arabinose-inducible promoter. Through oral administration of the modified bacteria and arabinose, in situ controllable production of OMVs loaded with tumor antigen in the intestine was achieved. The OMV-based tumor vaccine not only overcame the intestinal epithelial barriers to reach the immune cells in the lamina propria, but also stimulated dendritic cell maturation to facilitate a potent antitumor adaptive immunity. The oral bacteria generated OMV-based tumor vaccine significantly inhibited the lung metastatic melanoma and subcutaneous colon cancer in mouse models. Furthermore, a robust immune memory was generated, offering long-term protection against tumor challenge. Our work provides a proof-of-concept for oral bacteria generated OMV-based tumor vaccine that may be further developed and translated into clinical use.