Two clinically approved chemotherapeutic drugs (doxorubicin and decitabine) were used in this study to construct a balanced, dual-targeting nanocarrier, which used hyaluronic acid-mediated targeted delivery to triple-negative breast cancer (TNBC) cells and targeted TNBC stem cells to achieve effective treatment of TNBC growth and metastatic roots. This dual-drug nanocarrier could synergistically induce the upregulation of Gasdermin E through DNA demethylation, while activating Caspase-3 through mitochondrial damage. Thus, this study achieved targeted pyroptosis in TNBC cells that are refractory to pyroptosis, thereby enhancing immunogenic cell death and significantly activating antitumor immunity, demonstrating great potential for clinical application. The work was mainly completed by PhD candidate Lan Yang.