We found that Radix Astragali acts on several hub targets that can prolong the survival time of osteosarcoma patients, thus regulating the signaling network formed by several signaling pathways, than achieved the effect of regulating the biological behavior of osteosarcoma cells, such as proliferation, apoptosis, migration, and infiltration, etc. Among the drug ingredients of Radix Astragali, quercetin has the most potential to become an anti-osteosarcoma drug, while the hub targets PPARG, RXRA, and ESR1 are the most potential therapeutic targets when Radix Astragali acting on osteosarcoma. This evidence concerns the gene RXRA and osteosarcoma.