Our results demonstrated that the AUC of PLAU1 was 0.8328 (95% CI, 0.7677–0.8979; sensitivity: 76.25%; specificity: 80.00%) and PLAU1 was correlated with metastatic lymph nodes, T stage and UICC stage HNSCC patients, while the AUC of MMP1 was 0.9059 (95% CI, 0.8613–0.9506; sensitivity: 81.25%; specificity: 80.00%) and MMP1 was correlated with T stage and UICC stage in HNSCC patients. This evidence concerns the gene MMP1 and head and neck squamous cell carcinoma.