Objective To analyze the signals of adverse event (AE) of ripretinib by using the US FDA Adverse Event Reporting System (FAERS) database, and to provide reference for the clinical rational use of ripretinib.Methods Reporting odds ratio (ROR) and proportional reporting ratio (PRR) methods were used to mine the adverse reaction signals of ripretinib reported in the FAERS database from the second quarter of 2020 to the fourth quarter of 2023. The AE descriptions were standardized using the system organ classification (SOC) and preferred term (PT) of the Medical Dictionary for Regulatory Activities (MedDRA) version 26.1, and signals shared by ROR and PRR methods were screened for analysis.Results A total of 2 869 adverse event reports were obtained, of which the proportion of female patients (54.02%) was higher than that of male patients (43.71%). Among patients of known age, the reported AE cases were mainly concentrated in ≥65 years old. A total of 141 effective signals were obtained, involving 20 SOC categories, including general disorders and various reactions at the drug administration site, skin and subcutaneous tissue disorders and gastrointestinal disorders, etc. PTs with high frequency included fatigue, alopecia, disease progression, etc. And PTs with high signal strength included tumor compression, skin keratosis, freckles. In addition, a total of 152 adverse event signals which were not mentioned in the instructions were discovered, including muscle spasms, dry skin, asthenia, pain in extremity, and weight loss.Conclusion In the clinical use of ripretinib, the pharmaceutical care should be strengthened, and the regular monitoring should be conducted. Be alert to the occurrence of AEs not mentioned in the instructions, such as muscle spasms, dry skin, asthenia, pain in extremity, and weight loss, etc. If any related AEs occur, timely intervention measures should be taken to ensure the safety of medication for patients.