Head and neck squamous cell carcinoma (HNSCC) are referred to a group of heterogeneous cancers that include structures of aerodigestive tract such as oral and nasal cavity, salivary glands, oropharynx, pharynx, larynx, paranasal sinuses, and local lymph nodes. HNSCC is characterized by frequent alterations of several genes such as TP53, PIK3CA, CDKN2A, NOTCH1, and MET as well as copy number increase in EGFR, CCND1, and PIK3CA. These genomic alterations play a role in terms of resistance to chemotherapy, molecular targeted therapy, and prediction of patient outcome. MicroRNAs (miRNAs) are small single-stranded noncoding RNAs which are about 19-25 nucleotides. They are involved in the tumorigenesis of HNSCC including dysregulation of cell survival, proliferation, cellular differentiation, adhesion, and invasion. The discovery of the stable presence of the miRNAs in all human body made them attractive biomarkers for diagnosis and prognosis or as targets for novel therapeutic ways, enabling personalized treatment for HNSCC. In recent times the number of papers concerning the characterization of miRNAs in the HNSCC tumorigenesis has grown a lot. In this review, we discuss the very recent studies on different aspects of miRNA dysregulation with their clinical significance and we apologize for the many past and most recent works that have not been mentioned. We also discuss miRNA-based therapy that are being tested on patients by clinical trials.