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Background The purpose of this study was to investigate the prognostic value of the pretreatment inflammatory markers platelet-to-lymphocyte ratio (PLR) and the neutrophil-to-lymphocyte ratio (NLR) in patients with head and neck squamous cell carcinoma (HNSCC). Methods We conducted a retrospective analysis of patients diagnosed with HNSCC at McGill University Health Center from 2000 to 2011 (273 patients were retained). Hematologic parameters were recorded within 4 weeks of diagnosis. Mortality and recurrence rates were compared according to various PLR and NLR thresholds. Results Of the total patients, 20.5% died and 11.0% had disease recurrence. PLR >170 was associated with higher mortality ( p = .008). The subgroup with a combination of PLR >170 and NLR ≤3.0 was associated with higher T classification and highest mortality (43%). NLR above 4.2 predicted higher rates of recurrence ( p < .0001). The NLR/PLR combination was at least as good as TNM staging in predicting survival. Conclusion PLR is an independent predictor of mortality; NLR is an independent predictor of recurrence in HNSCC. These parameters might be used to identify advanced stages rapidly and economically. © 2014 Wiley Periodicals, Inc. Head Neck 37: 103-110, 2015 [ABSTRACT FROM AUTHOR]