Objective To study the safety profile of dupilumab using the U. S. Food and Drug Administration Adverse Event Reporting System (FAERS) database and to mine the potential adverse event signals, so as to provide reference for rational clinical drug use. Methods The dupilumab-related adverse event records were selected by searching the FAERS database from the second quarter of 2017 to the second quarter of 2020 and standardizing dupilumab's drug name, with the primary suspected drug as a restriction. Potential adverse event signals were mined using the disproportionality analysis, including reporting odds ratio (ROR) and information component (IC), and MedDRA 23.0 was used to systematically classify the results. Results A total of 97 205 dupilumab-related adverse event records out of 16 684 618 data records were obtained. According to the results of 2 adverse event signal mining methods, 365 adverse event signals were obtained under the restricted conditions of the lower limit of the ROR value 95% confidence interval (CI) >1 or the lower limit of the IC value 95% CI >0. Finally, 82 adverse event signals with greater clinical significance were obtained through the removal of non-adverse events and the merger of the same name, and the adverse events of dupilumab were mainly eye, skin and subcutaneous diseases, infections and infestations. The adverse event signals leading to serious adverse event outcomes mainly included eye diseases, infections and inflammations that may be caused by the drug, accelerated deterioration of cutaneous T-cell lymphoma, hypersensitivity of immune system, bronchitis of respiratory system, arthralgia and systemic diseases of skeletal system, and deterioration of various reactions at the site of administration. The top 5 drugs were prednisone, cyclosporine, treprostinil, prednisolone and methotrexate among the total adverse events and serious adverse events of drug combination. Conclusion In addition to the mild and moderate shallow corneal damage and conjunctivitis, clinicians should pay attention to the more serious eye detection signals such as corneal degeneration and ulcerative keratitis. It is also recommended to conduct a medical assessment with the ophthalmologist to instruct patients on medication. Doctors need to be more vigilant in medicine for patients with original eye problems. The adverse reaction signals detected by other systems still require long-term monitoring of adverse drug reactions of real-world medications. The outcome of serious adverse events of dupilumab and the corresponding detection signals, as well as the medications in combination with the most adverse events are worthy of attention.