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This study aimed to investigate the relationship and potential mechanisms of miR‐200c‐5p in colorectal cancer (CRC) progression. Differentially expressed miRNAs were screened using the TCGA database. Subsequently, univariate analysis was performed to identify CRC survival‐related miRNAs. Survival and receiver operator characteristic curves were generated. The target genes of miR‐200c‐5p and the relevant signaling pathways or biological processes were predicted by the miRNet database and enrichment analyses. The miR‐200c‐5p expression was detected using quantitative reverse‐transcription polymerase chain reaction, Cell Counting Kit‐8, Transwell, and cell apoptosis experiments were performed to determine miR‐200c‐5p's impact on CRC cell viability, invasiveness, and apoptosis. Finally, we constructed a CRC mouse model with inhibited miR‐200c‐5p to evaluate its impact on tumors. miR‐200c‐5p was upregulated in CRC, implying a favorable prognosis. Gene set enrichment analysis revealed that miR‐200c‐5p may participate in signaling pathways such as the TGF‐β signaling pathway, RIG‐I‐like receptor signaling pathway, renin‐angiotensin system, and DNA replication. miR‐200c‐5p potentially targeted mRNAs, including KCNE4 and CYP1B1, exhibiting a negative correlation with their expression. Furthermore, these mRNAs may participate in biological processes like the regulation of intracellular transport, cAMP‐dependent protein kinase regulatory activity, ubiquitin protein ligase binding, MHC class II protein complex binding, and regulation of apoptotic signaling pathway. Lastly, miR‐200c‐5p overexpression repressed the viability and invasiveness of CRC cells but promoted apoptosis. The tumor size, weight, and volume were significantly increased by inhibiting miR‐200c‐5p (p < 0.05). miR‐200c‐5p is upregulated in CRC, serving as a promising biomarker for predicting CRC prognosis. [ABSTRACT FROM AUTHOR]