Micro- and nano-meter size particles have become popular candidates for cancer vaccine adjuvants. However the mechanism by which such particles enhance immune responses remains unclear. Here we report a porous silicon microparticle (PSM)-based cancer vaccine that greatly enhances cross-presentation and activates type I interferon response in dendritic cells. PSM-loaded antigen exhibited prolonged early endosome localization and enhanced cross-presentation through both proteasome- and lysosome-dependent pathways. Phagocytosis of PSM by dendritic cells induced type I interferon responses through a TRIF- and MAVS-dependent pathway. Dendritic cells primed with PSM-loaded HER2 antigen produced robust CD8 T cell-dependent anti-tumor immunity in mice bearing HER2-positive mammary gland tumors. Importantly, this vaccination activated tumor immune microenvironment with elevated levels of intra-tumor type I interferon and MHC-II expression, abundant CD11c+ dendritic cell infiltration, and tumor-specific cytotoxic T cell responses. These findings highlight the potential for PSM as an immune adjuvant to potentiate dendritic cell-based cancer immunotherapy.