Background There have been cases reporting anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) and associated serious gastrointestinal (GI) adverse drug reactions (gastrointestinal obstruction, perforation, and ulceration). These adverse drug reactions are not in the drug package inserts, and the drug relationships are not proven in the literature. Aim We aimed to examine the potential association between GI obstruction, perforation, and ulceration, and ALK-TKIs by data mining of the US FDA Adverse Event Reporting System (FAERS). Method We conducted a disproportionality analysis of GI obstruction, perforation, and ulceration by estimating the reporting odds ratios (ROR) and the information component (IC) with 95% confidence intervals. Results A total of 279 cases of ALK-TKI-associated GI obstruction, perforation, and ulceration from January 1, 2011, to December 31, 2020, were identified. GI obstruction, perforation, and ulceration cause 16% of cases of death. A significantly increased reporting rate for GI obstruction [ROR 1.77 (1.45-2.15); IC 0.82 (0.53-2.03)] and perforation [ROR 1.61 (1.28-2.02); IC 0.68 (0.35-1.92)] was observed for ALK-TKIs as a drug class. The signal of GI ulceration was detected only in crizotinib [ROR 1.23 (1.01-1.50); IC 0.29 (0.01-1.51)]. A statistically significant ROR and IC emerged for the site of the esophagus. Conclusion Overall, the pharmacovigilance study of the FAERS indicates slightly increased reporting of GI obstruction and perforation, which may cause severe or even fatal outcomes among ALK-TKIs users.