In conclusion, in this study, we found that MEG3 could aggravate imatinib-induced cardiomyocyte injury by targeting the miR-129-5p/HMGB1 axis through in vitro experiments, indicating that MEG3 may be involved in the development of cardiotoxicity during TKIs treatment, and may be a potential target to alleviate myocardial toxicity for the patients with cancer. The gene discussed is HMGB1; the disease is cancer.