In recent years, the human oral microbiome has emerged as a significant target of interest and research focus because of the role microbiota in oral cavity may play in the progression, diagnosis, and treatment of diseases. Home to an abundant and distinct network of microorganisms that include viruses, fungi, protozoa, and over 700 species of bacteria, only the human gastrointestinal tract harbors more microbiota than the oral microbiome. Although recent advances in genomic sequencing technologies have made it possible to study the involvement between oral bacterial communities and cancer, the role of the oral microbiome in head and neck squamous cell carcinoma remains poorly defined and understood. This review will highlight what is known to date about the connections between the oral microbiome and head and neck cancer.