OBJECTIVE Cystic echinococcosis (CE) is a zoonotic disease that causes fluid-filled cysts in internal organs and is a major public health problem worldwide. The lack of standardized methods for the diagnosis/follow-up of CE disease necessitates the development of new non-invasive diagnostic tools, such as the determination of changes in the expression levels of circulating microRNAs (miRNA). In this study, we aimed to investigate the presence of miR-146a in archived serum samples of CE patients for the first time and to evaluate its potential role in the diagnosis and follow-up of CE over a three-year period. METHODS This study included archived serum samples from 39 CE patients, 56 follow-up samples from 14 CE patients, and 3 healthy controls, and expression levels of miR-146a were evaluated in each group using quantitative real-time polymerase chain reaction. Due to the small and unbalanced control group, bootstrapped confidence intervals were used; time-dependent changes in follow-up patients were analyzed using a linear mixed-effects model and Welch’s F test to address variance heterogeneity. RESULTS The miR146 gene was found to be significantly upregulated in archived serum samples of patients with CE compared to healthy control samples. Additionally, the expression level of the miR146 gene in follow-up serum samples significantly decreased in the third year post-surgery compared to follow-up blood samples taken in previous years (p<0.05). CONCLUSION According to the obtained results, it was concluded that miR-146a can be recommended as a diagnostic biomarker in the diagnosis and follow-up of CE, and archived materials of CE patients can be utilized in new biomarker research.