Background: Head and neck squamous cell carcinoma (HNSCC) has the sixth-highest incidence rate of all malignant tumors. The occurrence and progress of HNSCC are induced by extensive molecular changes, resulting in a poor prognosis. The present study aims to explore how altered microRNAs (miRNAs) and their co-expression networks of miRNAs-target mRNAs in HNSCC and to provide references for diagnosis and therapy research. Methods: The reported miRNAs that were ectopically expressed in HNSCC were partly summarized and classified according to the research outcomes. Next, the target mRNAs of miRNAs were predicted using data from online databases. Following that, the co-expression networks between miRNAs and target mRNAs were constructed using Cytoscape. Next, a series of functional enrichment analyses were completed using online databases. Results: A total of 132 miRNAs were summarized using data retrieved from the published literature and then were classified into three grades: A [92], B [18], C [22], according to the research content. Based on these grades, the target mRNAs of the miRNAs in each grade were predicted through data from online databases, and the co-expression networks were constructed separately. Functional enrichment analyses showed that miRNAs participated in multiple molecular functions, biological processes, and signaling pathways. The PI3K-Akt, MAPK, and Wnt signaling pathways, were determined to be regulatory pathways of epithelial-mesenchymal transition (EMT), for instance. Conclusions: A total of 132 altered miRNAs took part in the regulation of the PI3K-Akt, MAPK, Wnt signaling pathways, and other significant pathways or functions. The present study suggests that miRNAs might be key biomarkers for the diagnosis and therapy of HSNCC.