Chemical carcinogens derived from cigarettes and other tobacco products, as well as betel quid, paan, and alcohol consumption, are commonly associated with head and neck cancer risk. This is a particularly debilitating cancer, with a high recurrence rate and long-term treatment comorbidities affecting health and lifestyle. Controlling tobacco access or use may be an ideal prevention strategy but may also be challenging or undesired. Individuals, however, may be able to reduce their risk through simple and focused dietary change. Results from epidemiologic studies, basic research, and clinical investigations suggest that a diet rich in cruciferous vegetables may increase carcinogen metabolism, induce apoptosis, and reduce the risk of developing a primary head and neck tumor. This review briefly summarizes head and neck cancer nutritional epidemiology, and then describes the biochemical and epidemiologic literature describing the effects of crucifer consumption on head and neck carcinogenesis. To translate these findings, the strengths and limitations of specific intervention models are discussed, including differences in target populations and the choice of a food-based or pill-based approach for intervention. Addressing these factors in a future intervention may define a low-cost and non-toxic approach to reduce the burden of head and neck cancer.