Acupuncture is an important part of Chinese medicine that has been widely used in the treatment of inflammatory diseases . During the coronavirus disease 2019 (COVID-19) epidemic, acupuncture has been used as a complementary treatment for COVID-19 in China . However, the underlying mechanism of acupuncture treatment of COVID-19 remains unclear . Based on bioinformatics/topology, this paper systematically revealed the multi-target mechanisms of acupuncture therapy for COVID-19 through text mining, bioinformatics, network topology, etc . Two active compounds produced after acupuncture and 180 protein targets were identified . A total of 522 Gene Ontology terms related to acupuncture for COVID-19 were identified, and 61 pathways were screened based on the Kyoto Encyclopedia of Genes and Genomes . Our findings suggested that acupuncture treatment of COVID-19 was associated with suppression of inflammatory stress, improving immunity and regulating nervous system function, including activation of neuroactive ligand-receptor interaction, calcium signaling pathway, cancer pathway, viral carcinogenesis, Staphylococcus aureus infection, etc . The study also found that acupuncture may have additional benefits for COVID-19 patients with cancer, cardiovascular disease and obesity . Our study revealed for the first time the multiple synergistic mechanisms of acupuncture on COVID-19 . Acupuncture may play an active role in the treatment of COVID-19 and deserves further promotion and application . These results may help to solve this pressing problem currently facing the world.