Abstract: This study aimed to investigate the activity and mechanism of Citri grandis Exocarpium-Cordyceps militaris compound on reliving cough by the use of network pharmacology. Mouse cough inducing models were constructed by ammonia water to evaluate the cough suppressant activity of the compound. Multiple online databases and literature searches were then used to collect the active ingredients, targets of action and disease targets of the compound. Construction of compound-target-disease networks and protein interaction networks using Cytoscape and STRING, and GO and KEGG enrichment analysis of target genes using Meatscape. The results showed that the low and high dose groups significantly reduced the number of coughs in mice (P<0.001) and decreased the levels of three inflammatory factors, tumor necrosis factor, interleukin 1α and interleukin 1β in mice serum, with significant differences in the high dose group (P<0.05, P<0.01, P<0.05). The results of the network pharmacological analysis showed that this compound could act on 78 targets including transcription factor AP-1, interleukin 6 and tumor necrosis factor, regulating 575 GO entries and 272 signalling pathways to exert cough suppressant effects, of which cordycepic acid, cordycepin, apigenin, beta-sitosterol and naringenin were the important material basis. The results indicated that the combination of Citri grandis Exocarpium-Cordyceps militaris has cough suppressant activity, which was the result of the combined action of multiple substances in the combination on multiple targets and pathways.