Adverse event reports submitted to the US Food and Drug Administration (FDA) were analyzed to map the safety profile of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). We conducted a disproportionality analysis of the adverse events (AEs) of EGFR-TKIs (gefitinib, erlotinib, afatinib, osimertinib) by data mining using the FDA adverse event reporting system (AERS) database, and by calculating the reporting odds ratios (ROR) with 95% confidence intervals. The FDA AERS database contained 27,123 EGFR-TKI-associated AERs within the reporting period from January 1, 2004 to March 31, 2018. Thirty-three preferred terms (PTs) were selected for analysis, and significant RORs were most commonly observed in the skin, nail, gastrointestinal tract, hepatic, eyes, and lungs. Unexpected adverse drug reactions were found in the "intestinal obstruction" and "hypokalaemia" in gefitinib and erlotinib, "hyponatraemia" in gefitinib, erlotinib and afatinib, "alopecia"in erlotinib, "hair growth abnormal" in afatinib, but not in "nausea" and "vomiting" listed on drug labels. The results of this study are consistent with clinical observation, suggesting the usefulness of pharmacovigilance research should be corroborated with the real-world FAERS data.