Abstract： Objective： To explore the mechanism of Tripterygium Wilfordii Radix in preventing and treating ankylosing spondylitis （AS） based on network pharmacology and molecular docking. Methods： The chemical components of Tripterygium Wilfordii Radix were retrieved from the TCSMP database. The targets of its chemical components were predicted using the Pharmmapper database. AS-related targets were screened through the CTD and Genecard databases. The protein-protein interaction（PPI） network was constructed and analyzed topologically using the String database. Core targets were screened using six algorithms in the hubba plugin of Cytoscape software. GO and KEGG enrichment analyses of the targets were conducted using the Metascape database. The core component-core target-core signaling pathway network of Chinese medicinals was constructed via the Cytoscape software， by visualization and analysis of key targets and signaling pathways of Tripterygium Wilfordii Radix. Molecular docking was performed via Discovery Studio Client 19.1.0 software. Results：The active components of Tripterygium Wilfordii Radix that regulate autophagy to prevent and treat AS are Tripchlorolide， Salazinic acid， Triptoditerpenic acid B， Triptofordin C2， and Triptofordin F2. The core targets include serum albumin （ALB）， matrix metalloproteinase 9 （MMP9）， insulin-like growth factor 1（IGF1）， estrogen receptor （ESR1）， the heat shock protein 90α family A member 1 （HSP90AA1），matrix metalloproteinase 2 （MMP2），and mitogen-activated protein kinase （MAPK1） . The main signaling pathways include the phosphatidylinositol 3-kinase and protein kinase B （PI3K/AKT） interaction pathway， resistance mechanisms to epidermal growth factor receptor tyrosine kinase inhibitors， MAPK1 signaling pathways， the interleukin-17 （IL-17） signaling network，and T-helper 17 （Th17） signaling pathways. Conclusion： Tripterygium Wilfordii Radix may prevent and treat AS by affecting enzyme-linked receptor protein signaling pathways and inflammatory responses.