Abstract: The individualized management of tyrosine kinase inhibitor (TKI)-related intolerance in chronic myeloid leukemia (CML) remains a clinical challenge. The present case report concerns an elderly male patient with chronic-phase CML who developed grade 3 hematological toxicity and drug-induced liver injury after imatinib therapy and remained intolerant despite dose reduction. Subsequent switches to flumatinib and nilotinib were discontinued due to progressive elevation of liver enzymes and gastrointestinal adverse events. A stepwise reduction in the dosage of dasatinib was initiated, resulting in the achievement of a deep molecular response (MR4.0; BCR-ABLIS≤0.01%) and the reversal of liver fibrosis within a period of four months. This case demonstrates the necessity to dynamically evaluate efficacy and toxicity during TKI therapy and promptly adjust treatment regimens. The toxicity profiles of TKIs exhibit significant interindividual variability: flumatinib demonstrates lower hepatotoxicity but prominent gastrointestinal effects, nilotinib may aggravate liver fibrosis, and dasatinib balances efficacy and safety through dose optimization. For patients with limited financial resources, dose-reduction strategies employing second-generation TKIs constitute a viable alternative. This case study offers practical insights into individualized management for patients with multi-line TKI intolerance.