Single-cell RNA sequencing (scRNA-seq) is a novel method enabling genetic characterization of tumor tissue at a single-cell level. This study systematically reviewed the literature on studies using scRNA-seq to characterize head and neck squamous cell carcinomas (HNSCCs). Seven studies were included, of which two studies performed scRNA-seq on 20 patients in total, and five studies used scRNA-seq data in a subsequent clinical study. The former mentioned two studies found intra-tumoral genetic heterogeneity among malignant cells but genetic uniformity among non-malignant cells. The five latter studies used scRNA-seq data in various ways. Three studies identified biomarkers related to predicting whether a patient would benefit from immunotherapeutic treatment. One study characterized genes related to the perineural invasion. One study identified genes to be used in diagnostics. Further studies performing scRNA-seq on HNSCC are required to continue the ongoing development and use of scRNA-seq.