Background. Ankylosing spondylitis (AS) is a rheumatism that mainly affects the axial bones and joints. Xinfeng capsule (XFC) is a preparation with a remarkable clinical effect that is used in our hospital. And it has definite curative effect and less side effects in the treatment of AS. Objective. Data mining and network pharmacology were used to analyze the efficacy of Chinese medicine Xinfeng capsule on treating the hypercoagulable state of ankylosing spondylitis and the underlying mechanism behind it. Methods. Clinical data were collected and compiled from the Department of Rheumatology and Immunology of the First Affiliated Hospital of Anhui University of Chinese Medicine. Cluster analysis was used to investigate herbs that frequently used to treat AS, Apriori module was used to analyze the association rules between herbs and laboratory indexes, and the random walk model was used to reveal the therapeutic efficacy of XFC against AS. The TCMSP database was used to acquire the active components and targets of XFC, and the GeneCards and OMIM database were used to obtain the targets of AS. Afterward, an active ingredient‐target network was established and core targets were screened for; overlapping targets were screened for the protein‐protein interaction (PPI) network analysis, the Gene Ontology (GO) enrichment analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Molecular docking was adopted to investigate the interactions between main active components and core targets. Results. Frequently used herbs could be divided into three groups, and according to the analysis of Apriori module, there is a strong correlation between XFC and the improvement of ESR and hs‐CRP, and the results of the random walk model demonstrated that the effect of XFC on improving PLT, ESR, and hs‐CRP was superior to the use of traditional Chinese medicine alone. In total, 103 active compounds of XFC and 59 overlapping targets were obtained. The PPI relationships were obtained through the STRING database, and 13 core targets were identified. 1786 GO enrichment results and 205 KEGG enrichment results were obtained, including NF‐kappa B signaling pathway, TNF signaling pathway, and IL17 signaling pathway. The outcomes of molecular docking revealed a close relationship between the active compounds of XFC and core targets. Conclusion. This study demonstrated that XFC can effectively improve the hypercoagulable state and the inflammatory indices of AS patients through data mining, and it has a strong correlation with the clinical improvement of inflammation. The active compounds of formononetin, triptolide, quercetin, and kaempferol may be the key active components of XFC in regulating AS, possibly through inhibiting the activation of NF‐kappa B signaling pathway to improve hypercoagulable state.