Abstract: Objective To explore the expression of P53 protein in the surgical margins of patients with head and neck squamous cell carcinoma （HNSCC）, and its relationship between clinicopathological parameters and tumor local recurrence. Methods The expression of P53 protein in 82 cases of human HNSCCs and 10 cases of normal oral mucosa was detected by using immunohistochemistry. The correlations among P53 protein to clinicopathological parameters and tumor local recurrence in these cases was investigated. Results Of the 82 cases of HNSCC, 59.76% (49/82) in surgical margins were positive for P53 protein. P53 protein was mainly detected in nucleus of basal cell in surgical margins. The expression of P53 protein was significantly higher in surgical margins of patients with HNSCC than that in normal oral mucosa (P<0.05). P53 protein positive expression was significantly correlated with tumor differentiation and tumor local recurrence in 82 cases of HNSCC (P<0.05), but not with age and gender of patients, pathological stage, lymph node metastasis and anatomic site of tumor were not found (P>0.05). Conclusion These results suggest that the presence of P53 protein in tumor surgical margins correlates with the development of HNSCC after operation. P53 protein may serve as one prognostic factor for tumor local recurrence.