MicroRNAs (miRNAs) play important roles in regulation of proliferation, migration, and invasion of head and neck squamous cell carcinoma (HNSCC). The present study assessed expression, functions and mechanisms of miR‑20a‑5p in the regulation of HNSCC cell proliferation, migration and invasion. miR‑20a‑5p expression in HNSCC cell lines and tissues was detected using qRT‑PCR, while miR‑20a‑5p mimics and inhibitor were transfected into HNSCC cells for assessment of the effects using different assays (CCK‑8, wound healing and Transwell assays) and expression of miR‑20a‑5p‑targeting genes (using western blot and luciferase reporter assays). The data revealed that miR‑20a‑5p was upregulated in both HNSCC tissues and metastatic HNSCC cells. Upregulated miR‑20a‑5p expression in HNSCC cells promoted tumor cell proliferation, migration and invasion capacities, but resulted in downregulation of TNFRSF21 expression and in turn upregulation of C‑C motif chemokine receptor 7 (CCR7) in HNSCC cells. Concordantly, knockdown of miR‑20a‑5p in HNSCC had the opposite results. In conclusion, miR‑20a‑5p functioned as an oncogene in HNSCC by downregulating TNFRSF21 and subsequently, upregulating CCR7 expression.