Background The prognostic roles of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been reported in head and neck squamous cell carcinoma (HNSCC), but their results remain controversial. Methods A total of 25 literatures with 28 cohorts involving 6847 HNSCC patients were included. The hazard ratio (HR) was pooled with 95% confidence interval (CI) using fixed-effects or random-effects models. Results High pretreatment NLR predicted poor overall survival (OS: HR = 1.68; 95% CI = 1.39-2.03; P < .001), disease-free survival (DFS: HR = 1.76; 95% CI = 1.42-2.17; P < .001), progression-free survival (PFS: HR = 1.53; 95% CI = 1.09-2.14; P = .014), and cancer-specific survival (CSS: HR = 1.45; 95% CI = 1.23-1.71; P < .001) in HNSCC. However, the association between PLR and OS or DFS was not statistically significant. Conclusion The NLR can serve as a potential prognostic biomarker for patients with HNSCC.