Objective To characterize the expression patterns of serum microRNA-497 （miR-497） in patients with colorectal cancer （CRC） and to investigate its associations with clinicopathological characteristics， diagnostic performance， and long-term prognostic outcomes. Methods This study retrospectively analyzed data from 122 patients with CRC admitted to the hospital between March 2020 and March 2022 （CRC group）， and enrolled 100 healthy individuals undergoing routine physical examinations （healthy control group） for comparison. Serum samples were collected from all participants prior to any surgical intervention， and the expression levels of miR-497 in serum were quantified using real-time quantitative polymerase chain reaction （qRT-PCR）. Simultaneously， the levels of carcinoembryonic antigen （CEA） and carbohydrate antigen 199 （CA199） were measured. To investigate the association between miR-497 expression and clinicopathological characteristics， we evaluated its diagnostic performance using receiver operating characteristic （ROC） curve analysis. Furthermore， Kaplan-Meier survival analysis and Cox proportional hazards regression models were employed to assess its impact on patient prognosis. Results Compared to healthy individuals， CRC patients exhibited significantly lower serum miR-497 expression levels （P < 0.001）. Notably， miR-497 expression was strongly correlated with TNM stage progression and lymph node metastasis （P < 0.001）， but showed no significant association with tumor location， patient sex， or age. Diagnostic evaluation using ROC curves demonstrated that miR-497 achieved an AUC of 0.845 for CRC detection， outperforming CEA （AUC = 0.748） and CA19-9 （AUC = 0.702）， with DeLong′s test confirming the statistically significant differences （P < 0.05）. Kaplan-Meier survival analysis revealed a significantly higher 3-year DFS rate among patients with high miR-497 expression （84.06%） compared to those with low expression （64.58%）， with median DFS not reached in the high-expression group versus 36 months in the low-expression group （P = 0.015）. Multivariate Cox regression analysis confirmed that reduced miR-497 expression （HR = 1.923， 95% CI： 1.184 ~ 3.125）， advanced TNM stage （HR = 2.511， 95% CI： 1.421 ~ 4.437）， and lymph node metastasis （HR = 1.753， 95% CI： 1.151 ~ 2.664） were independently associated with poorer disease-free survival outcomes. Conclusions Serum miR-497 is downregulated in patients with CRC and is significantly associated with tumor progression and poor prognosis. It demonstrates high diagnostic accuracy and strong potential for prognostic evaluation， highlighting its promise as a biomarker for auxiliary diagnosis and outcome prediction in CRC.