Abstract：Objective：To analyze the medication patterns and mechanisms of topical Chinese medicine for handfoot syndrome （HFS） by integrating data mining and network pharmacology. Methods：Literature on Chinese medicine external treatment of HFS published from databases inception to June 30，2024 was retrieved from CNKI，Wanfang， VIP，Google Scholar，and PubMed to build a prescription database. Excel 2021，IBM SPSS Modeler 18.0，and SPSS Statistics 27.0 were used to analyze herb frequency， properties， flavors， and meridian tropism， association rule analysis， and clustering analysis. Network pharmacology was applied to identify key targets of the core herb-pair “Astragali Radix-Angelicae Sinensis Radix-Cinnamomi Ramulus” for HFS. A protein-protein interaction （PPI） network was constructed；GO and KEGG enrichment analyses were performed. Molecular docking between core active components and key targets was carried out using AutoDockTools. Results：A total of 160 herbs were included；19 were of high frequency， among which Angelicae Sinensis Radix， Cinnamomi Ramulus， Astragali Radix， Carthami Flos， and Chuanxiong Rhizoma were most frequently used. The dominant properties were warm， cold， and neutral； the dominant flavors were bitter， pungent， and sweet； most herbs entered the liver meridian. Association-rule analysis yielded 85 rules with support ≥ 10% and confidence ≥ 88%. Clustering analysis produced five herb combinations. The core herbal triplet “Astragali Radix-Angelicae Sinensis Radix-Cinnamomi Ramulus” contained 62 active components and 81 HFS-related targets. Network topology identified 7-O-methylisomucronulatol，dihydroisoflavone，3-hydroxy- 9， 10-dimethoxypterocarpan， medicarpin， and sphingosine as key components. PPI analysis highlighted G1/Sspecific cyclin-D1 （CCND1）， epidermal growth factor receptor （EGFR）， cysteine-aspartic protease 3 （CASP3）， signal transducer and activator of transcription 3 （STAT3）， and heat-shock protein 90α family class A member 1 （HSP90AA1） as hub targets. KEGG analysis revealed that the main signaling pathways involved the cancer pathway， hypoxia-inducible factor-1 （HIF-1）， forkhead box O （FoxO）， and mitogen-activated protein kinase （MAPK）. Molecular docking showed that the binding energies between the core active components and the key targets were mostly < -5 kcal/mol. Conclusion：Topical Chinese medicine for HFS focuses on herbs that activate blood and resolve stasis. The core herbal triplet “Astragali Radix-Angelicae Sinensis Radix-Cinnamomi Ramulus” exerts therapeutic effects via multi-component，multi-target，and multi-pathway mechanisms involving anti-inflammation，modulation of cell proliferation/apoptosis，and alleviation of oxidative stress.