<p>Breast cancer ranks as the most prevalent cancer worldwide. MicroRNAs (miRNAs) play dual roles as oncogenes and tumor suppressors, requiring their detailed investigation in tumor tissues. This study intended to assess the expression of less explored hsa-miR-497-5p and hsa-miR-17-5p in Indian breast cancer patients, their comparative roles, and their relationship to clinicopathological features. The archived formalin-fixed paraffin-embedded (FFPE) blocks of 74 breast tumors and 36 adjacent normal breast tissue specimens were analyzed. Expression levels of hsa-miR-497-5p and hsa-miR-17-5p were quantified by quantitative real-time PCR and correlated with clinicopathological characteristics and then compared to the publically accessible TCGA-BRCA dataset. Potential target genes of these miRNAs were identified using five prediction programs, followed by protein-protein interaction (PPI) network and Gene Ontology (GO) enrichment analysis using suitable in silico tools. The expression analysis showed a significant increase in hsa-miR-17-5p levels and a decrease in hsa-miR-497-5p in breast tumors than the normal tissues. The receiver operating characteristic (ROC) curve demonstrated the hsa-miR-497-5p with a higher diagnostic value (AUC = 0.95) than miR-17-5p (AUC = 0.69). The decreased expression level of hsa-miR-497-5p in TCGA-BRCA and FFPE samples emphasizes its role as a tumor suppressor and potential predictive biomarker for breast cancer. In contrast, miR-17-5p overexpression emphasizes its oncogenic function and role in tumor progression, making it a viable therapeutic target. The hsa-miR-497-5p exhibits a higher diagnostic value than hsa-miR-17-5p. In conclusion, hsa-miR-497-5p and hsa-miR-17-5p could be biomarkers to serve diagnostic and prognostic purposes, supported by their differential expression profiles and in silico analyses of predicted target genes and pathways.</p>