Recent advances in technology and the evolution of bioinformatics are enabling progress in the development of new therapeutic cancer vaccine strategies. Whilst these advancements have vastly improved the specific antigenic component of vaccine design there remains an unmet need for the incorporation of appropriate adjuvants to ‘boost’ the desired immune response. Given the powerful immunomodulatory capacity of type I interferons (IFN) in both anti-viral and anti-tumour immunity, we asked whether members of this cytokine family could enhance potent tumour-specific CD8+ T cell immunity when incorporated into vaccine protocols. A whole-cell anti-cancer vaccine strategy was devised whereby mice were immunised with irradiated tumour cells genetically engineered to secrete a single IFN subtype. Each of the IFN subtypes were screened for their potential to enhance CD8+ T cell expansion 7 days post-vaccination when compared to vaccination alone. IFNβ was identified as the superior adjuvant candidate performing significantly better than all IFNα subtypes tested and also the current gold-standard cancer vaccine adjuvant, poly(I:C). In response to vaccination with IFNβ, we observed significant increases in tumour-specific CD8+ T cell priming, activation and recruitment to the tumour microenvironment. A crucial role for cross-presenting XCR1+ dendritic cells and CD4+ T cell immunity in mediating this augmented immune response was identified. Furthermore, CD40/CD40L signalling is necessary for optimal T cell immunity, whereas NK cells were not required. Therapeutically, combination therapy with IFNβ vaccination and anti-PDL1 checkpoint blockade treatment resulted in increased cancer immunosurveillance and could significantly delay tumour progression. This data provides strong rationale for incorporating IFNβ as a natural adjuvant into future vaccine protocols. Furthermore, the power of IFNβ to remarkably improve anti-tumour immunity could have significant implications in other immunotherapies and ultimately lead to greater success rates.