Bone metastasis in prostate cancer can occur decades after primary tumour diagnosis. Latency associated with bone metastasis has been widely attributed to tumour cell dormancy – a state in which tumour cells can survive undetected for prolonged periods. One mechanism proposed to induce dormancy in bone is tumour immune surveillance, suggesting metastatic outgrowth may require tumour cell-driven immune evasion strategies. Our lab has identified that immune evasion and subsequent metastasis in breast cancer may be facilitated by tumour cell suppression of type I Interferon (IFN) signalling via the downregulation of key IFN regulatory factors. Importantly, we have now demonstrated that IFN signalling is lost in bone metastases compared to matched primary tumours in prostate cancer patients. To interrogate timing of loss, we utilised the murine C57BL/6 RM model of prostate cancer linked to a cell labelling technique to FACS-purify dormant and proliferating RM cells from bone for RNA sequencing. Single-cell analysis revealed that the expression of several key mediators of IFN signalling were retained in dormant, yet lost in active RM cells derived from bone metastases. Suppression of tumour-intrinsic IFN signalling in active RM cells was shown to be bone-specific compared to primary tumours and tumour cells derived from other metastatic sites, can be induced within 48 hours of contact with bone stroma, and can be reversed using chromatin modulatory agents. It was also demonstrated that loss of tumour-intrinsic IFN signalling is sufficient to significantly accelerate tumour progression to bone and increase metastatic burden. Furthermore, we have shown systemic IFN inducers can significantly reduce metastatic progression via enhanced immune cell activation when tumour-intrinsic IFN signalling is intact. Overall, these novel results suggest that loss tumour-intrinsic IFN signalling is bone specific, is a critical event preceding metastatic outgrowth from dormancy and suppresses immune activation required for an effective anti-tumour response. This work may be exploited therapeutically to decrease metastasis in prostate cancer with the potential to reduce patient mortality.