Background: Measurement of minimal residual disease (MRD) in bone marrow is a powerful predictor of relapse in acute lymphoblastic leukemia (ALL). MicroRNAs are secreted in urine or saliva at levels that mirror the cellular state and function, showing potential as non-invasive biomarkers for predicting MRD status. We aimed to assess the usefulness of circulating microRNAs in saliva and urine as MRD biomarkers in pediatric ALL. Procedures: The study population included patients under 18 diagnosed with ALL at a national referral pediatric hospital in Lima, Peru. Saliva and urine were collected on day 15 of induction chemotherapy. Patients were stratified into high-risk (HRR) or standard intermediate-risk (SIRR) groups of relapse based on MRD at day 15. Small RNA Sequencing and RT-qPCR were used to identify and validate differentially expressed microRNAs. Results: Thirty miRNAs were differentially expressed in saliva and 2 in urine. Both miRNAs differentially expressed in urine were downregulated. Notably, miR-1246, miR-223-3p, and miR-1290 exhibited the highest upregulation in the HRR group in saliva (Log 2 FC = 4.00, 3.95, and 3.73, respectively). Upon validation, the upregulation of miR-223-3p in saliva was confirmed (Log 2 FC = 1.19, p = 0.025). Both miR-223-3p alone and the combination with miR-1290 and miR-1246 demonstrated the best performance in distinguishing between HRR and SIRR patients (AUC = 0.71, 95 % CI: 0.55-0.86, and AUC = 0.72, 95 % CI: 0.57-0.87, respectively). Conclusions: These preliminary findings suggest that miR-222-3p, either alone or in combination with miR-1246 and miR-1290, could potentially serve as non-invasive MRD biomarkers in pediatric ALL.