Periplogenin is a compound extracted from cortex periplocae. In the monomers' screening for inhibiting nasopharyngeal carcinoma, we found that periplogenin can inhibit nasopharyngeal carcinoma; however, its mechanism is still unclear. In this study, the chemical structure of periplogenin was uploaded to the PubChem database in order to obtain the target of periplogenin. The NPC's differential genes were obtained by analyzing the nasopharyngeal carcinoma data in the GEO database by R software. The common target of periplogenin and nasopharyngeal carcinoma was obtained through Cytoscape. Through R software analysis, ALB, epidermal growth factor receptor (EGFR), MAPK1, ESR1, MAPK8, SRC, CASP3, HSP90AA1, AR, MAPK14 may be the main targets of periplogenin in NPC. Through go enrichment analysis, it was found that periplogenin acted mainly on nasopharyngeal carcinoma through response to steroid metabolic process, cellular response to steroid hormone stimulus, hormone-mediated, and steroid hormone signaling pathway. After enrichment analysis on the Kyoto Encyclopedia of Genes and Genomes pathway, it was found that periplocan may inhibit NPC through the MAPK signaling pathway (the main signaling pathway), and the signaling pathway of proteoglycans in cancer, and the PI3K/AKT signaling pathway as well. In this study, we also carried out the experimental study of vitamin E together with periplogenin self-assembled nano-prodrugs in the treatment of NPC, and the results showed that tumor weight of PBS group was 0.531±0.039 g, while that of PPG group and MPSSV-NPs group was 0.258±0.059 g and 0.169±0.033 g, respectively, which was lower than PBS group. And the tumor inhibition rate of MPSSV-NPs was 69.41%, which was significantly higher than that of the PPG group (51.38%). This study demonstrated the mechanism of inhibition of nasopharyngeal carcinoma (NPC) by the monomer of periplogenin based on network pharmacology. We preliminarily confirmed that vitamin E coupled with a periplogenin self-assembled nano-prodrug has obvious effect in treating nasopharyngeal carcinoma.