AIM: Crizotinib, an anaplastic lymphoma kinase tyrosine kinase inhibitor (ALK-TKI). It gained approval from the U.S. Food and Drug Administration (FDA) specifically for treating ALK-positive non-small cell lung cancer (NSCLC). The objective of the present investigation was to evaluate adverse events (AEs) associated with crizotinib in real-world by employing data mining on the U.S. FDA Adverse Event Reporting System (FAERS). METHODS: Data encompassing AEs linked to crizotinib from 2011 to 2023 were gathered. Disproportionality analyses, which involved the utilization of reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS), were employed for analytical purposes. RESULTS: A total of 10,226 reports documenting crizotinib-associated AEs were extracted from the FAERS database. Out of these, 147 preferred terms (PTs) displaying significant disproportionality were identified concurrently across all four algorithms. The most frequently observed AEs included increased transaminases, bradycardia, prolonged QT, nausea, vomiting, diarrhea, constipation, visual impairment, and interstitial lung disease, which were consistent with previous reports from clinical trials. Additionally, unexpected significant AEs such as deep vein thrombosis, pneumocystis jirovecii pneumonia, gastrointestinal amyloidosis, and hepatic coma were also observed. CONCLUSION: Crizotinib offers therapeutic benefits but is also accompanied by various risks in the form of AEs. Our study findings align with previous clinical observations, and furthermore, we have identified unforeseen serious AEs. This discovery serves as a novel basis for the monitoring of dosages and the identification of risks associated with crizotinib.