Immunotherapy is a promising new approach for tumor treatment. However, its clinical application is hindered by insufficient immunogenicity, hypoxia, and immunosuppressive tumor microenvironment (TME). Here, oxygen pump microneedles (OPMNs) loaded with zinc-doped copper sulfide nanoflowers (ZCS NFs) and PD-L1 small interfering RNA (siPD-L1) (OPMNs-ZCS@siPD-L1) are developed for boosting tumor immunotherapy. OPMN-ZCS@siPD-L1 enhances tumor immunogenicity through ZCS NFs by inducing cuproptosis, reverses TME through siPD-L1, and promotes drug penetration, and ameliorates hypoxia through oxygen bubbles. More importantly, cuproptosis-induced mitochondrial DNA (mtDNA) together with Zn