Functional analyses identified associations with oncogenic pathways, with UBE2D1 expression positively correlated with MMP2 and negatively correlated with SMAD4, indicating a potential role in tumor progression.<h4>Conclusion</h4>UBE2D1 is frequently overexpressed in HNSCC and is associated with adverse clinical outcomes. Here, MMP2 is linked to head and neck squamous cell carcinoma.