Sex determining region Y-box 2 (SOX2) has been identified as a putative cancer stem cells (CSCs) marker in Head and Neck Cancers (HNC). However, the clinicopathological and prognostic significance of SOX2 in HNC patients remains controversial. We reviewed the literature by performing a meta-analysis based on the data from 7 studies (9 cohorts) to evaluate the association between SOX2 and clinicopathological/prognostic parameters in patients with HNC. Pooled hazard ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) was used as the effect size estimate. Our analysis results suggested that high SOX2 expression predicted unfavorable OS (HR: 1.54, 95% CI: 1.09-2.18) and DFS (HR: 1.54, 95% CI: 1.13-2.10) of patients with HNC. In addition, increased SOX2 was also significantly associated with high tumor grade (OR: 1.86, 95% CI: 1.06-3.28), advanced TNM stage (OR: 4.22, 95% CI: 2.62-6.80), lymph node metastasis (OR: 2.25, 95% CI: 1.50-3.35) and distant metastasis (OR: 1.99, 95% CI: 1.26-3.15). Our study suggested that SOX2 expression can be served as a candidate unfavorable prognostic biomarker for HNC patients, indicating that it might be a potential therapeutic target.