Triple-negative breast cancer (TNBC) remains the second most-life-threatening carcinoma to women worldwide. Compared to conventional chemotherapeutic drugs, natural compounds, especially curcumin (CUR), have been proven to have therapeutical potential in TNBC treatment. To improve the accumulation of CUR at tumor sites, a reactive oxygen species (ROS)-responsive nanocarrier was developed (CUR@Bio/PE-NPs) with CUR entrapment and biotin conjugation, exhibiting a strong affinity for breast cancer cells. CUR@Bio/PE-NPs demonstrated a particle size of 142.9 nm, good stability, and an encapsulation efficiency of 63.67%, while realizing a positive feedback loop of ROS-accelerated CUR release and CUR-induced ROS generation in tumor cells. In vitro studies revealed that CUR@Bio/PE-NPs induced ROS generation effectively and promoted ∼1.30and 1.36-fold cellular uptake of Nile red@Bio/PE-NPs compared to nontargeted nanoparticles in MDA-MB-231 and 4T1 cells, respectively. In addition, CUR@Bio/PE-NPs suppressed their proliferation (IC 50 , MDA-MB-231:3.277 μg/mL, 4T1:5.259 μg/mL) with increased apoptosis and cell cycle arrest while preventing cell-migration and invasion. Importantly, in a 4T1 tumor xenografted mice model, nanoformulation prolonged curcumin accumulation at tumor sites, modulated the tumor immune microenvironment and prevented tumor growth and lung metastases without significant toxicity. In short, the in vitro and in vivo results suggested CUR@Bio/PE-NPs as a promising strategy for TNBC therapy.