Abstract: This study developed hyaluronic acid (HA)-modified, ginsenoside Rg₃-loaded hollow mesoporous MnO₂ nanoparticles (HMR@HA) and evaluated their characterization, in vitro release, and anti-triple-negative breast cancer efficacy. Hollow mesoporous MnO₂ nanoparticles (HM) were synthesized by template method. HMR nanoparticles were prepared by loading ginsenoside Rg₃, and then targeted HMR@HA system was constructed through HA modification. Laser particle size analysis, transmission electron microscopy (TEM), and Fourier transform infrared spectroscopy (FTIR) were used to characterize the samples. High-performance liquid chromatography (HPLC) quantified Rg₃ loading capacity and assessed HMR@HA's in vitro release profile. We evaluated the uptake capacity of 4T1 cells for nanoparticles and the in vitro antitumor activity of nanoparticles. The experimental results indicate that the optimal preparation parameters are: the mass ratio of drug to carrier of 5∶1, the stirring time of 12 h, and the drug concentration of 10 mg·mL^-1. The obtained HMR@HA exhibits the uniform hollow structure with a particle size of 216.3 ± 1.3 nm and the loading capacity is (42.42 ± 2.55)%. The release curve shows pH dependence, and the cumulative release gradually increases as the pH decreases. The results showed that HMR@HA was efficiently taken up by 4T1 cells and significantly inhibited the proliferation and migration of cancer cells. Active oxygen and mitochondrial membrane potential detection showed that HMR@HA can promote tumor cell apoptosis. HMR@HA has a high drug loading capacity and pH-sensitive drug release properties. Compared with ginsenoside Rg₃, it significantly enhances antitumor activity and induces apoptosis, providing an effective treatment strategy for triple-negative breast cancer.