ObjectiveTo explore the effective components and mechanism of Epimedii Folium in the treatment of oligoasthenotspermia by using network pharmacology and molecular docking technique. MethodThe main active components and corresponding target genes of Epimedii Folium were screened out from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. Target genes of oligospermia were obtained by GeneCards and Online Mendelian Inheritance in Man （OMIM） database. Uniprot was used to correct all genes. The drug-active component-key target regulatory network was constructed by Cytoscape3.9.0， and the key active components were screened out according to the degree value. The active components and common targets of the disease were uploaded to STRING 11.5 database to construct the Epimedii Folium and oligoasthenotspermia target protein-protein interaction （PPI） network， and the key protein targets were screened out according to the degree value. The key targets of gene ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed using DAVID database. Protein Data Bank （PDB） and TCMSP were used to obtain the molecular structure of target proteins and active components. AutoDock Vina 1.1.2 was used to perform molecular docking of the active components and the core protein targets. Finally， icariin， the active component of Epimedii Folium， was used to intervene in the rat model of oligoasthenotspermia to verify the effect of icariin on the expression level of protein targets. ResultTwenty-three active components from Epimedii Folium were screened out， and 50 common targets and 6 core targets of oligoasthenotspermia and Epimedii Folium were obtained， including tumor protein p53 （TP53）， epidermal growth factor receptor （EGFR）， prostaglandin-endoperoxide synthase 2 （PTGS2）， cysteine aspartate-specific protease （Caspase）-3， erb-b2 receptor tyrosine kinase 2 （ERBB2）， and caspase-9. Through GO enrichment and KEGG pathway enrichment analysis， the active components of Epimedii Folium were mainly involved in the P53 signaling pathway， the pathways in cancer， cell proliferation， and apoptosis， etc. Molecular docking results indicated that icariin， quercetin， and 8-isopentenol had strong binding ability to target protein. The results of icariin intervention experiment showed that as compared with the control group， the expression of target proteins in testis of rats with oligoasthenotspermia was significantly down-regulated. As compared with the model group， icariin significantly up-regulated the expression of target protein in testis of rats with oligoasthenotspermia （P<0.05）. ConclusionEpimedii Folium treats oligoasthenotspermia through regulating the P53 signaling pathway， the pathways in cancer， cell proliferation， and apoptosis by icariin， quercetin， and 8-isopentenol.