OBJECTIVE: To explore the risk factors for cardiotoxicity in patients with gastrointestinal (GI) tumors treated with fluorouracil drugs. METHODS: This study included patients with GI tumors who received fluorouracil at our hospital between January 2018 and April 2022. The demographic and clinical characteristics were collected. The risk factors associated with the cardiotoxicity of fluorouracil were explored using multivariable logistic regression. RESULTS: A total of 300 patients were finally included and divided into the cardiotoxicity ( CONCLUSION: Hyperlipidemia, diabetes, older age, treatment with capecitabine, and adjuvant radiotherapy might be independent risk factors for the cardiotoxicity of fluorouracil in patients with GI tumors.