<h3>Objectives</h3> To understand the role of the tumor-stroma ratio (TSR) in head and neck squamous cell carcinoma (HNSCC) and to evaluate its prognostic value. <h3>Study Design</h3> An electronic search was performed in PubMed/Medline, Web of Science, Science Direct, Scopus, Embase, and Cochrane Collaboration Library databases. Articles that assessed the relationship between TSR and HNSCC prognosis through analysis of global and/or disease-specific survival were included in the assessment. The quality of evidence was assessed using the Newcastle-Ottawa scale. <h3>Results</h3> After applying the inclusion and exclusion criteria, 9 articles were included. Data from present systematic review indicate that, in squamous cell carcinomas (SCC) of the esophagus and oral cavity, stromal-rich tumors showed lower survival, being TSR associated with high recurrence rates locoregional in the oral cavity and considered an independent prognostic factor for esophageal disease-free survival. Furthermore, a high proportion of stroma in oral SCC was significantly associated with the depth of invasion, pattern of tumor invasion, perineural invasion, location, and size of the primary tumor. <h3>Conclusions</h3> This study demonstrated a strong relationship between TSR and the prognosis in SCC of esophagus and oral cavity.