In summary, our findings suggested the presence of the circRFWD3/miR-27a/b /PPARγ/NF-κB/MMP13 axis in regulating HNSCC metastasis, highlighting the potential of circRFWD3 as a novel therapeutic target in HNSCC metastasis. The gene discussed is NFKB1; the disease is head and neck squamous cell carcinoma.