Oral cancer cells are derived from normal oral mucosal keratinized epithelium. As with all malignancies, oral cancer occurs as a result of DNA mutations, which are often spontaneous. The incidence of DNA mutations is significantly higher when exposed to carcinogenic factors such as physical, chemical or microbial agents. The etiology of oral squamous cell carcinoma has been extensively studied. Etiologically, there are many risk factors that promote the development of this type of malignant lesion. Several important carcinogenic factors have been identified, among which tobacco and alcohol are considered to be the most important factors in the development of malignant lesions. Both extrinsic and intrinsic factors may play a role in the occurrence and development of oral squamous carcinoma. The incidence of oral cancer is 2-12 times higher in smokers than in non-smokers, and 90% of oral cancer patients have a history of smoking. The combination of two factors, smoking and thermal irritation, can lead to epithelial degeneration of the upper gastrointestinal tract. Chewing betel nut and other mixtures can cause increased basal cell division activity of oral mucosa epithelium, which increases the incidence of oral cancer. Alcohol has a pro-carcinogenic effect and can also act as a solvent for carcinogens, promoting the entry of carcinogens into the oral mucosa. The patient’s own genetic susceptibility coupled with this progressive degeneration can manifest as different degrees of expression of tumor suppressor genes or pathogenic genes, leading to tumor development. Poor oral hygiene and local chronic irritation also have a relationship with the occurrence of oral cancer. Poor oral hygiene creates conditions for bacteria or mycobacteria to breed and multiply in the oral cavity, thus facilitating the formation of nitrosamines and their precursors. Coupled with stomatitis, some cells are in proliferative state and more sensitive to carcinogens, these reasons may promote the occurrence of oral cancer. The roots or sharp tips of teeth or unsuitable dentures that irritate the oral mucosa for a long time can also produce chronic ulcers and even cancer. Research has demonstrated that certain viruses may also play a role in oral carcinogenesis, particularly human papillomavirus (HPV). HPV has been found to have a strong association with cervical cancer, and a similar association has been found in studies of oral cancer. Studies have shown that oral HPV-infected individuals are 3.7 times more likely to develop cancer than uninfected individuals when other factors are excluded, and in particular, recent studies on the relationship between HPV16 and oral cancer have shown a more pronounced correlation in Western populations in the mid-term, which may be closely related to some of their lifestyle habits. Genetic mutations are an important cause of oral cancer. A variety of physical, chemical or microbial stimuli can activate oncogenes or suppress oncogenes, and abnormal regulation of oncogenes can lead to functional mutations, for example, in squamous carcinoma, transforming growth factor alpha (TGF-α) and eukaryotic translation initiation factor 4E (eIF4E) are two genes that have been well studied and confirmed to be upregulated. The absence of both normal alleles in tumor suppressor genes results in the loss of some important functions of such genes and thus the loss of tumor suppressor gene function. The most studied tumor suppressor genes include P53 and P169, and the development of cancer is often the result of a combination of mutations in multiple genes rather than a single mutation. The current research in this area has yielded some results. It is expected that gene therapy for oral cancer will be an important direction in the near future.