Background:Next-generation sequencing (NGS) is a powerful tool that has enabled the systematic study of genomes and provided researchers with insights into disease understanding. NGS is a massive and parallel DNA sequencing technology for large-scale, ultra-high throughput, and automated high speed genome analyses.NGS has a wide variety of applications for the study of biological systems at a new level.NGS-applied OSCC research has also identified various genetic alterations and detected mutations with low variant allele frequency. Aim: This paper aims to systematically review next generation based microRNA sequencing in Oral Squamous cell carcinoma Methods: A search was done using MeSH terms and keyword search in the electronic databases namely PubMed, Google Scholar, Cochrane, Science Direct ,Lilacs and addition searches were carried out through cross checking the bibliographies of selected articles. Then based on the inclusion and exclusion criteria and availability of the full texts, a total of 2 articles were included in this systematic review Result:The search yielded a total of articles out of which 56 articles were included based on the eligibility criteria. Quality assessment based on the Quality Assessment of Diagnostic Accuracy Studies 2 tool was used to obtain a risk of bias chart using Revman 5.4 software and it was proved that from the 2 included studies, one had low risk of bias and another had moderate risk of bias. Conclusion:This systematic review aimed at improving the current understanding of next generation sequencing and applicability in OSCC. Further, this may be an alleyway for the identification of newer biomarkers using NGS-based technique.