Objective To analyze the adverse drug reaction (ADR) signals of bortezomib through mining data from the USA FDA Adverse Event Reporting System (FAERS), and to provide references for the safe use of bortezomib in clinical practice.Methods The reporting odds ratio (ROR) and proportional reporting ratio (PRR) methods were used for signal detection of the bortezomib-related adverse events reported in FAERS from the first quarter of 2004 to the fourth quarter of 2019 (64 quarters in all).Results A total of 18 389 signals with bortezomib-related adverse events were obtained, with the median age of 65 years, and the male to female ratio was 1.29∶1. The related reports from physician accounted for 48.3% (8881/18 389) and that from the USA accounted for 48.3% (8890/18 389). Among the reports, intravenous administration and subcutaneous injection were the main routes of administration, accounting for 41.9%. Nearly 25% of cases died. Among the top 50 reported adverse events with detected signal, plasma cell myeloma, lower hemoglobin, bone marrow failure, increased blood creatinine, muscle weakness, and hypokalemia had not been included in bortezomib specification.Conclusion There were far more male patients weighing more than 75 kg than female patients, suggesting that body weight may be related to the adverse reactions of bortezomib. The patients with bortezomib-related adverse events were mainly over 65 years old, indicating that the elderly were more likely to have adverse reactions. The causality of the bortezomib-related adverse reactions that have not yet been included in its specification can be further studied, and the impact of these adverse reactions on the original disease should be monitored.