Abstract： Objective： To explore the action mechanism of Fritillariae Thunbergii Bulbus-Sepiae Endoconcha drug pair for gastroesophageal reflux disease (GERD) based on network pharmacology. Methods： The active components of Fritillariae Thunbergii Bulbus-Sepiae Endoconcha were screened through Traditional Chinese Medicines Systems Pharmacology Platform (TCMSP)， BATMAN-TCM， Chinese medicine and active ingredients，Ben Cao Zu Jian-HERB databases and related literature. SWISS ADME and SwissTargetPrediction platform were used to predict active ingredient targets. GeneCards， DisGeNET and Drugbank were used to screen the targets of GERD； the intersection targets of Fritillariae Thunbergii Bulbus-Sepiae Endoconcha drug pair and GERD were obtained through Jvenn Platform，and the intersection targets were uploaded to STRING11.0 database. Cytoscape3.7.1 software was used to construct protein interaction network diagram to obtain the core targets of Fritillariae Thunbergii Bulbus- Sepiae Endoconcha drug pair for GERD treatment； Genetic Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed for core targets using Metascape database；AutoDock tools was used to verify the molecular docking between key components in drug pairs and core targets. Results： A total of 28 active ingredients of Fritillariae Thunbergii Bulbus- Sepiae Endoconcha durg pairs，536 medicine targets and 1 997 GERD targets were screened out. The core active components of Fritillariae Thunbergii Bulbus-Sepiae Endoconcha drug pairs included Peiminine， Zhebeirine， Picropodophyllin， etc.； the core targets of Fritillariae Thunbergii Bulbus-Sepiae Endoconcha drug pairs in the treatment of GERD included serine/threonine-protein kinase (AKT1)， mitogen-activated protein kinase (MAPK) 1， phosphatidylinosiol 3-kinase catalytic domain δ(PIK3CD)， epidermal growth factor (EGFR)， proto-oncogene (JUN) and so on. Fritillariae Thunbergii Bulbus-Sepiae Endoconcha medicine pairs mainly act on neuroactive ligand-receptor interaction， phosphatidylinositol 3 kinase (PI3K)/ protein kinase B (AKT)， MAPK and cancer signal pathways in the treatment of GERD. Molecular docking showed that the core active ingredient Zhebeirine and Peiminine had higher binding activity to AKT1 and other targets. Conclusion： Fritillariae Thunbergii Bulbus-Sepiae Endoconcha drug pairs can act on the AKT1，EGFR and other targets to treat GERD，and its mechanism of action is related to the regulation of neuroactive ligand-receptor interaction，PI3K/Akt signal，MAPK signal pathway and other signal pathways.