Prior studies of squamous cell carcinoma of the head and neck (SCCHN) have explored the effect of socioeconomic status (SES) as an independent risk factor; however, none have investigated the interaction of known risk factors with SES. We examined this using the North Carolina Head and Neck Cancer Epidemiology Study, a population-based case–control study. Incident cases of SCCHN from North Carolina between 2002 and 2006 (n = 1,153) were identified and age, sex, and race-matched controls (n = 1,267) were selected from driver license records. SES measures included household income, educational attainment, and health insurance. Logistic regression was used to estimate adjusted odds ratios (OR) and 95 % confidence intervals (CI). Current smoking was more strongly associated with SCCHN among those households making < $ 20,000/year OR 5.11 (3.61–6.61) compared to household incomes > $ 50,000/year OR 2.47 (1.69–3.25); p interaction < 0.001. Current drinking was more strongly associated with SCCHN in household incomes < $ 20,000 OR 2.91 (2.05–3.78) compared to > $50,000/year 1.28 (0.97–1.58); p interaction < 0.001. Current drinkers with less than high school education or income < $20,000 had nearly threefold odds of never-drinkers in the same SES category OR 2.91 (2.05–3.78); 2.09 (1.39–2.78), respectively. Our results suggest that the relationship of smoking and alcohol use may be stronger among those of lower SES.