Background: Liver cancer is one of the most lethal cancers globally, with current treatments offering limited efficacy and significant side effects. Astragaloside II (ASII), a compound derived from traditional Chinese medicine, shows promise in reducing adverse effects, improving patient constitution, and prolonging survival. However, its clinical application is hindered by poor solubility and distribution. This study aims to develop a neutrophil-based nanocarrier system to enhance the tumor-targeting capability and therapeutic efficacy of ASII. Methods: We encapsulated ASII within PEG-PLGA nanomicelles and loaded them into neutrophils to create a neutrophil nanocarrier system (PG@AS-Neu). The physical properties of PG@AS-Neu were characterized using dynamic light scattering (DLS) and transmission electron microscopy. The encapsulation efficiency and release profile of ASII were investigated using high-performance liquid chromatography. The inhibitory effects of ASII and PG@AS-Neu on liver cancer cells were evaluated through cell viability, apoptosis, scratch wound, Transwell, and hemolysis assays to assess the nanocarrier’s biosafety. Results: The neutrophil nanocarrier system demonstrated excellent stability and intact cellular morphology. Hemolysis assays confirmed the nanocarrier’s blood compatibility. Cell viability, apoptosis, and invasion and migration assays revealed that both ASII and PG@AS-Neu significantly inhibited liver cancer cells. The preparation process of PG@AS-Neu did not compromise the anticancer activity of ASII, showing similar efficacy to free ASII. Conclusion: PG@AS-Neu exhibits potent anticancer effects and holds significant potential for liver cancer treatment.