Objective Chronic Myeloid Leukemia (CML) is a myeloproliferative disorder characterized by the BCR-ABL fusion gene, which leads to constitutive tyrosine kinase activity and results in uncontrolled cell proliferation. This genetic alteration causes increased cell growth and suppression of apoptosis. The aim of this study is to investigate the effects of the natural compounds silymarinand kaempferol on the expression of 88 cancer-related miRNAs and genes associated with apoptosis and cell cycle regulation in the K562 CML cell line. Methods K562 cells were treated with the IC₅₀ doses of silymarin and kaempferol for 48 hours. Following total RNA (including miRNA) isolation, the expression levels of 88 miRNAs as well as apoptosis- and cell cycle-related genes were evaluated using quantitative PCR. Expression changes were analyzed using the 2^-ΔΔCT method, and fold changes ≥2 or ≤−2 were considered statistically significant (p<0.05). Results Both compounds significantly altered the expression of several miRNAs. Tumor-suppressor miRNAs were generally upregulated, while oncogenic miRNAs such as miR-21 were downregulated. Among apoptosis-related genes, CASP3, BAX and TP53 were upregulated, whereas BCL2 was downregulated. Additionally, cell cycle regulatory genes such as CDK1 and CCNB1 were also found to be downregulated. Conclusion Kaempferol and silymarin exhibited anticancer potential in CML by modulating miRNA profiles and regulating genes involved in apoptosis and cell cycle processes. These findings suggest that both compounds may serve as potential adjunct therapeutic agents in the treatment of Chronic Myeloid Leukemia.