Background: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm with a prevalence of one to two patients per 100,000 adults. This investigation aimed to assess the clinical significance of microRNA-21 in CML & its role as a predictor of therapeutic response to tyrosine kinase inhibitors (TKI) in an Egyptian patient. Patients and methods: This case-control research has been performed on ninety cases; forty-five of them had chronic myeloid leukemia, fifteen of them had recently been diagnosed with chronic myeloid leukemia, fifteen patients on Imatinib, fifteen patients on second-generation TKI after failure of Imatinib, & 45 healthy controls. Patients were selected from internal medicine & hematology clinics in Beni-Suef University Hospital and Kasr-Alini Hospital in the period between April 2022 and April 2023. Results: MicroRNA-21 had a statistically significant role in CML disease prediction. At a cutoff of 1.2 with 53% sensitivity& 88% specificity. Also, microRNA-21 had a statistically significant role in the therapeutic response to tyrosine kinase inhibitors. At a cutoff of 0.73 with 86% sensitivity& 66% specificity. Conclusion: In CML cases, miRNA 21 expression levels were significantly greater than those in controls. (1.68±1.26, 0.90±0.22) (p-value, 0.0001). The levels of miRNA-21 expression in CML patients decreased after ttt with TKI being higher in TKI resistance patients. there was no correlation between micro-RNA 21 expression &BCR-ABL after 6 months of Imatinib (p-value 0.465). No correlation has been observed between the expression of micro-RNA 21 & the Sokal score (p-value 0.423).