Objective: To mine the security alert signals of neratinib based on the FDA Adverse Event Reporting System (FAERS) database to provide a reference for the safety of clinical medication. Methods: The adverse drug event (ADE) signals data of neratinib from the FAERS database from the third quarter of 2017 to the third quarter of 2021 were collected. The data mining was performed using the reporting odds ratio (ROR) and the proportional reporting ratio (PRR) in the proportional imbalance method. Results: A total of 1 362 ADE reports with neratinib as the primary suspected drug were collected, and 96 neratinib ADE signals were mined; 71 signals were obtained after excluding non-adverse drug reaction signals, involving 13 systems. Among them, a total of 48 new signals were not mentioned in the instructions, accumulating 12 systems. Gastrointestinal disorders ADE entries totaled 2 186 cases, generating 25 signals; new signals from investigations accounted for 85.71% of their total system signals. Daily dose was not an independent risk factor for the occurrence of gastrointestinal disorders and investigations ADE. Logistic regression results showed that a course of treatment ≤7 days was an independent risk factor for the occurrence of gastrointestinal disorders, with statistically significant results (P=0.008); compared to a course of treatment ≤7 days, a course of treatment 1 to 3 months was an independent risk factor for the occurrence of investigations ADE (OR=4.288, 95% CI of 1.342 to 13.703;P=0.014). Conclusion: No matter what daily dose is used, adverse reactions need to be paid attention to. The duration of medication is of great significance to the risk of adverse reactions of neratinib, and pharmaceutical care should be strengthened during clinical medication.