(1) Background: Between tumors of the head and neck region, the squamous cell variant (HNSCC) is the most common and represents one of the main neoplasms affecting humans. At the base of carcinogenesis processes, there are genetic alterations whose regulation can be influenced by changes in the expression of microRNA (miR). Consequently, despite recent studies indicating miR-197 as a potential prognostic biomarker of survival for many varieties of cancer, there are currently no systematic reviews and trial sequential/bioinformatics/meta-analysis regarding the role of miR-197 in HNSCC. Our hypothesis was that with the existing literature, it is possible to clarify whether the different expressions of miR-197 in neoplastic tissues can represent a prognostic biomarker of survival in head and neck tumors. (2) Methods: The systematic review was reported following the indications of PRISMA and by consulting six electronic databases (including one register). Moreover, this review was carried out using the Kaplan-Meier plotter database portal, and hazard ratio (HR) data were extracted. Finally, a trial sequential analysis (TSA) was conducted to test the robustness of the proposed meta-analysis. (3) Results: This search identified 1119 articles and outcomes of the meta-analysis, reporting an aggregate HR for overall survival (OS) between the highest and lowest miR-197 expression of 1.01, 95% CI: [1.00, 1.02]. (4) Conclusions: We can state that, from the literature data included in the present meta-analysis, and from the TSA and bioinformatics analysis data, miR-197 does not currently represent a valid prognostic biomarker for HNSCC, although the data provided by the Kaplan-Meier plotter suggest that miR-197 can serve as a putative biomarker in short-term (5 years) survival.