Excision repair cross-complementation group 1 (ERCC1) protein has been extensively investigated as a prognostic and predictive factor for platinum-based treatment in head and neck squamous cell carcinoma (HNSCC) but with inconsistent results. We performed the present meta-analysis to better elucidate this issue in advanced HNSCC. A literature search was conducted using the PubMed and Web of Science databases. The inclusion criteria were head and neck cancer patients with platinum-based treatment and evaluation of the correlation between ERCC1 expression and clinical outcomes [objective response rate (ORR), progression-free survival (PFS), and overall survival (OS), both unadjusted and adjusted estimates]. In high vs. low pooled analyses, high ERCC1 expression was associated with unfavorable OS [hazard ratio (HR) = 1.95, 95 % confidence interval (CI) 1.18–3.21, p = 0.009], PFS (HR = 2.39, 95 % CI 1.74–3.28, p = 0.000) and ORR (odds ratio = 0.48, 95 % CI 0.23–0.98, p = 0.044). In the subgroup analysis of adjusted OS estimates, ERCC1 was a predictor of shorter survival in Asians (HR = 3.13, 95 % CI 2.09–4.70, p = 0.000) and Caucasians (HR = 2.02, 95 % CI 1.32–3.07, p = 0.001) but of longer survival in South Americans (HR = 0.17, 95 % CI 0.07–0.40, p = 0.000). Immunohistochemistry proved to be of predictive value irrespective of used antibody (p = 0.009). In the stratified analysis according to the tumor site, ERCC1 expression was associated with OS in nasopharyngeal cancer (HR = 2.72, 95 % CI 1.79–4.13, p = 0.000). ERCC1 has a potential to become predictive and prognostic factor enabling treatment tailoring in HNSCC patients.