Radiotherapy is an effective anti-cancer therapy for patients with non-small cell lung cancer (NSCLC), however, the prognosis is unsatisfactory owing to radio-resistance and toxicity. It is crucial to improve radiotherapy efficacy. Ag nanoparticles (NPs) and ginsenoside Rg3 (Rg3) exerted antitumor and radio-sensitization effects. Therefore, we investigated whether poly-lactide-co-glycolide-polyethylene glycol (PLGA-PEG)-Rg3-Ag will function as a noninvasive, tracing, radiotherapy sensitizer. The morphology of NPs was visualized with transmission electron microscopy (TEM). The drug loading content, encapsulation efficiency, and cumulative drug release of Rg3 was determined by HPLC. Cellular uptake of NPs in A549 and SPCA-1 was measured by immunostaining. The radio-sensitization effect of PLGA-PEG-Rg3-Ag in vitro was determined in A549 by detecting proliferation, colony formation, and apoptosis with CCK-8, clonogenic survival assay, and flow cytometry, while in vivo was determined in nude mice by testing the body weight and tumor volume. PLGA-PEG-Rg3-Ag exerted radio-sensitization effect by reducing cell proliferation and colony formation while enhancing cell apoptosis in A549; reduced tumor volume in nude mice. PLGA-PEG-Rg3-Ag exhibits radio-sensitization effects in NSCLC.