Microorganisms in the oral cavity are abundant in the human body. At present, more than 700 species of oral microorganisms have been identified. Recently, a lot of literature has indicated that the oral microbiota plays an important role in the occurrence, development, and prognosis of oral squamous cell carcinoma (OSCC) through various mechanisms. And researchers are now trying to utilize oral microbiota in cancer diagnosis and treatment. However, few articles systematically summarize the effects of oral microbes in the diagnosis, treatment, and disease outcomes of oral cancer. Herein, we made a summary of the microbial changes at cancerous sites and placed more emphasis on the mechanisms by which the oral microbiome promotes cancerization. Moreover, we aimed to find out the clinical value of the oral microbiome in OSCC.