Background: NPC (representing nasopharyngeal carcinoma) manifests stealthily, with pronounced invasiveness, resulting in most patients reaching an advanced stage by the time of their first diagnosis. AS-IV (short for “Astragaloside IV”), a major bioactive component in the traditional Chinese medicinal herb Huang Qi (Astragalus membranaceus), exhibits numerous pharmacological effects, including anti-cancerous effects and anti-inflammatory effects. SATB2 (short for “special AT-rich binding protein-2”) has been identified as a diagnostic marker for NPC. At present, the precise mechanism through which AS-IV regulates NPC aggravation remains unclear. Methodology: CCK-8 assays were performed to evaluate the impact of AS-IV on cell viability and identify the appropriate concentration gradients of AS-IV. AS-IV’s interferences with NPC cell transference, penetration, autophagy, and apoptosis were analyzed based on results from transwell assays, immunofluorescence (IF) assays, and flow cytometry (FCM) assays. Via western blotting, the content of SATB2 in NPC cells was tested and excess SATB2’s impacts on cellular biological traits were investigated. Besides, a Wnt signaling pathway blocking agent was administered to the SATB2-overexpressed NPC cells treated with AS-IV, followed by testing on the contents of proteins linked to the Wnt pathway. Further, subcutaneously transplanted NPC models were formed in nude mice to make clear the influence of AS-IV on in-vivo NPC expansion, alongside the testing of TUNEL-positive cell numbers in these tumor tissues. Results: Following the administration of AS-IV, the activity of NPC cells was diminished greatly, accompanied by inhibited cell transference, penetration, and autophagy, as well as driven cell apoptosis. However, this effect of AS-IV depended on its dosage. In NPC cells (especially in CNE-2 and 5-8F cells), SATB2 exhibited notably high contents. Once overexpressed, SATB2 partially prevented AS-IV from suppressing the aggravation of NPC cells. Upon treatment with AS-IV, NPC cells experienced a marked drop in the contents of proteins linked to the Wnt pathway; such contents however were elevated after overexpressing SATB2 but somewhat fell off with the further supplementation of DKK-1. Furthermore, AS-IV impeded in-vivo NPC expansion, and this impeding effect was offset partially following the heightening of SATB2 production. Conclusion: AS-IV deactivates the Wnt pathway by weakening the SATB2 production, thereby holding up NPC cells’ transference, penetration, and autophagy while fostering apoptosis.