Dysregulation of microRNAs (miRNAs) influences diverse hallmarks of cancer, including proliferative signaling, metastasis, and resistance to cell death. We explored the contribution of miR-92b-3p in oral squamous cell carcinoma (OSCC) and its potential as a monitoring biomarker. Analysis of TCGA, GEO, and our own cohort revealed dysregulation of miR-92b-3p in OSCC, which correlated with aggressive tumor characteristics. miR-92b-3p overexpression augmented proliferation and the epithelial-mesenchymal transition in both YD8 and SCC25 cell lines and xenograft models. Mechanically, augmented miR-92b-3p expression suppressed ATXN1 and CPEB3, activating the Notch signaling pathway and thereby promoting metastasis and cisplatin resistance. In our cohort, serum miR-92b-3p expression reflected the disease status, including relapse. Our results suggest that miR-92b-3p might be an onco-miR involved in OSCC through regulating the ATXN1/CPEB3/Notch pathway. These findings provide novel insights for treating and monitoring OSCC.