Abstract The tumour microenvironment (TME) causes mitochondrial dysfunction in resident dendritic cells (DCs), resulting in inadequate antigen presentation and weak T cell priming. Herein, we identify hypoxia as a key factor for causing pathological mitochondrial fission in tumour-associated DCs, and develop a plant vesicle-DC chimera to relieve hypoxia-induced mitochondrial dysfunction for enhancing cancer immunotherapy.