Cancers of the oral cavity are more common worldwide in men than in women, and the same is true for cancer of the nasopharynx region, whereby nasopharyngeal carcinoma (NPC) incidence rate in men is 2.5 times that in women. Different risk factors, including environmental, lifestyle and genetic factors, come into play in terms of contributing towards the development of these cancers. The increased incidence of oral cancers in developed countries in recent years are attributable to rises in the consumption of tobacco and/or alcoholic beverages, in addition to the traditional practice of betel quid chewing in some communities. As for NPC, the risk factors include male sex, overconsump-tion of preserved salted fish and smoking. In terms of etiology due to microbial agents, the human papillomavirus (HPV) has been linked with oral cancers whereby HPV DNA was found in about 2 out of 3 oropharyngeal cancer cases. In contrast, the Epstein-Barr virus (EBV) has been closely associated with most cases of NPC. Specifically, NPC is categorized by the WHO into two main histological types—keratinizing squamous cell carcinoma (type I) and non-keratinizing squamous cell carcinoma (types II and III), and it is the non-keratinizing type (types II and III) which has very high percentage of EBV DNA. The oncogenicity of these viruses had been studied extensively, and they are now recognized as crucial early triggers of NPC and oral cancers. Genetic factors can also predispose a person to the development of either oral cancer or NPC. Certain HLA class I alleles are associated with increased risks for NPC. Genetic polymorphisms in genes encoding the cytochrome P450 enzymes and glutathione S-transferase had been identified as potential risk factors for NPC. In our studies, we had shown that polymorphism in the XPD gene which encodes a DNA helicase enzyme involved in nucleotide excision repair was linked to risk for NPC in Malaysian population. We also found that the combination of CGC allele from hOGG1, ITGA2 and XPD polymorphisms was significantly associated with increased odds of NPC. In oral cancers, studies by other researchers revealed that gene polymorphisms in HOTAIR gene and the interaction with betel quid chewing are linked to oral cancer risk. Specific COX-2 gene polymorphisms were also found to be associated with increased risk for oral cancer development and progression. Taken together, these studies show a strong correlation between viral etiology combined with the indi-vidual’s genetic background coupled with certain risky lifestyle behaviours which together contribute towards the development of oral cancer and NPC.