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Abstract: Background: MicroRNAs (miRNAs) play crucial roles in head and neck squamous cell carcinoma (HNSCC). This study investigates whether miR‐31, miR‐96, and miR‐182 are involved in targeting Numb during HNSCC. Methods: The expression of miR‐31/96/182 in tumor tissues was analyzed. Reporter assay, knockdown, expression, and oncogenic analysis were carried out in cell lines. Results: Upregulation of miR‐31/96/182 was detected in tumor tissues. In addition, advanced tumors showed higher expression levels of these miRNAs. The expression of these miRNAs was upregulated after treatment with areca ingredients (P < .01 or P < .001). These miRNAs directly targeted the 3′ untranslated region (UTR) sequence of the Numb gene. An increased migration and invasion of HNSCC cells was associated with the exogenous expression of miR‐31/96/182 (P < .01 or P < .001), and this was reverted by expression of Numb. Conclusion: This study provides new evidence demonstrating that there is frequent and concordant upregulation of miR‐31, miR‐96, and miR‐182 during HNSCC and these miRNAs co‐target Numb. [ABSTRACT FROM AUTHOR]