This study investigated the immunodetection of CD57+ inflammatory cells in patients with head and neck squamous cell carcinoma (HNSCC) and its association with clinicopathological parameters and overall survival. Data collected from the morphological analysis and immunohistochemical reaction testing of archived HNSCC specimens (n=70) were statistically analyzed by bivariate and multivariate statistical testing at a significance level of P<0.05. The results indicate that CD57+ inflammatory cells predominate within the peritumoral stroma of HNSCC lesions and the existence of two significant relationships: between high CD57+ cell density and the development of a tumor of a large size [odds ratio (OR)=5.610, 95% confidence interval (CI)=1.516-20.763) and between high CD57+ cell density and the development of locoregional metastatic disease (OR=3.401, 95% CI=1.162-9.951). A significant difference in the rate of survival was detected only in HNSCC patients that presented large size tumors (OR=4.747, 95% CI=1.281-17.594). Together, these results suggest that although high CD57+ inflammatory cell density is associated with HNSCC lesions of greater clinical severity, the variable of cell density is not an independent predictor of HNSCC patient survival. Our findings also suggest that the relatively aggressive infiltration of CD57+ inflammatory cells in the peritumoral stroma of head and neck carcinomas may contribute to an ineffective locoregional antitumoral response.