BACKGROUND: Selinexor is approved for the treatment of relapsed or refractory multiple myeloma. However, a comprehensive understanding of adverse events associated with selinexor is lacking. METHODS: Clinical trials of selinexor in patients with multiple myeloma were reviewed. We investigated selinexor-related adverse events through data of the US Food and Drug Administration Adverse Event Reporting System (FAERS). The disproportionality analysis was conducted. Four algorithms were employed to evaluate the signals of adverse events. The adverse effects of selinexor combined with dexamethasone were compared with bortezomib and dexamethasone. Sensitivity analysis was performed to exclude consumer-reported adverse events. The onset of adverse reactions were calculated. RESULTS: A total of 1,698 reports related with selinexor from FAERS were identified. 6 significant system organ class and 42 significant preferred terms (PTs) were found. Unexpected significant adverse events including mania, acute kidney injury, orthostatic hypotension, and embolisms were identified. 14 PTs reported significant signals in treatment of selinexor combined dexamethasone compared with traditional treatment of bortezomib and dexamethasone. 45.2% of adverse events occurred within the first month of starting selinexor. CONCLUSIONS: Comprehensive analyses of selinexor related adverse events are helpful for clinical detection of adverse events and timely intervention, advancing selinexor's therapeutic progress in future treatment.