This study aimed to evaluate the association between several different aspects of disease in head and neck squamous cell carcinoma (HNSCC): morphological grading, Ki67 proliferation index (PI), invasive front, adjacent non-malignant mucosa (ANMM), recurrence and overall survival of the patients. Sixty-four fully reviewed and followed-up patients with primary HNSCC were matched according to recurrence of the lesion and placed in one of two groups of 32 cases. Chi-square and Fisher's exact tests were used to analyze the clinicopathological parameters between both groups of patients. Association between Ki67 PI and clinicopathological parameters was also analyzed through chi-square and Fisher's exact tests with the binary logistic regression model used as a multivariate analysis. In addition, survival analysis was also performed. Our results showed that high-risk dysplasia in ANMM and high Ki67 PI in ANMM of HNSCC exhibited a higher risk of tumor recurrence. Survival analysis showed that T3/T4 tumor sizes and high Ki67 PI were significantly associated with an increase in the risk of death in multivariate analysis. Our results revealed that high-risk dysplasia and high Ki67 PI of the ANMM are parameters which are indicative of tumor recurrence. Furthermore, T3/T4 tumor sizes and high Ki67 PI in the invasive front appear to be important prognostic tools for HNSCC.