Each tumor harbors unique repertoire of mutated antigenic peptides that are immunogenic and potentially can induce tumor-specific immune responses. Because heat shock proteins (HSPs) have the promiscuous ability to chaperone and present a broad repertoire of tumor antigens to antigen presenting cells, HSP tumor vaccine has been tested in clinical trials. However, this vaccine has many limitations, including individual preparation of HSP vaccines from each tumor ex vivo, and quantity of HSPs for therapy strictly limited by the size of the resected tumor mass. Hence, we developed a novel HSP-mediated oncolytic tumor vaccine, referred to as HOT vaccine, by combining the versatile ability of overexpressed HSPs to chaperone antigenic peptides and induce immune responses against a broad array of mutated tumor antigens, with the oncolytic activity of viruses. The results of this study demonstrate that intratumor vaccination with a recombinant oncolytic adenovirus overexpressing the HSP70 protein can eradicate primary tumors, as well as inhibit the growth of established metastatic tumor in mice. Because of its capacity to induce individual tumor-specific immune responses, this HSP-mediated oncolytic tumor vaccine might become a universally applicable, personalized vaccine against any type of solid tumor.