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The survival rate for head and neck cancer patients has not substantially changed in the last two decades. We previously showed that two rV- neu T intratumoral injections induced an efficient antitumor response and rejection of transplanted Neu (rat ErbB2/neu oncogene-encoded protein)-overexpressing salivary gland tumor cells in BALB- neu T mice (BALB/c mice transgenic for the rat ErbB2/neu oncogene). However, reiterated poxviral vaccinations increase neutralizing antibodies to viral proteins in humans that prevent immune response against the recombinant antigen expressed by the virus. Curcumin (CUR) is a polyphenol with antineoplastic and immunomodulatory properties. The aim of this study was to employ CUR administration to boost the anti-Neu immune response and anticancer activity induced by one rV- neu T intratumoral vaccination in BALB- neu T mice. Here, we demonstrated that the combined rV-n eu T+CUR treatment was more effective at reducing tumor growth and increasing mouse survival, anti-Neu humoral response, and IFN-γ/IL-2 T-cell release in vitro than the individual treatment. rV- neu T+CUR-treated mice showed an increased infiltration of CD4 + /CD8 + T lymphocytes within the tumor as compared to those that received the individual treatment. Overall, CUR enhanced the antitumoral effect and immune response to Neu induced by the rV- neu T vaccine in mice. Thus, the combined treatment might represent a successful strategy to target ErbB2/Neu-overexpressing tumors., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.