Aim: Metabolic acidosis subsequent to a high dietary acid load (DAL) leads to inflammation and cell transformation, which are common features of cancer development. Because the epidemiologic evidence associating DAL and cancer risk is still limited, we sought to explore the potential role of DAL as a risk factor for head and neck and oral cavity tumors. Methods: A case–control study was performed on 1126 men (563 cases and 563 age frequency and residence matched controls), drawn from the major public hospitals in Montevideo, Uruguay. Participants were interviewed through a multitopic questionnaire, including a food frequency questionnaire. Food-derived nutrients were calculated from available databases. DAL was calculated based on validated measures including potential renal acid load (PRAL) and net endogenous acid production (NEAP) scores. Odds ratios (OR) were estimated by logistic regression, adjusting for potential confounders. Results: We found significant and direct associations between dietary acid load and risk of head and neck and oral cavity cancers (OR = 2.10 and OR = 1.95 for highest PRAL and NEAP, respectively). In addition, stratified analyses by subsites displayed the highest estimates for pharyngeal cancer (OR = 2.40 and OR = 2.28 for highest PRAL and NEAP, respectively). No association was found for oral cavity cancers. Conclusions: An acidogenic diet may increase the risk of head and neck cancers. Our findings align well with our previous studies focused on other anatomic sites. Studies conducted on food groups and nutritional patterns align with our results. Further studies are needed to confirm these findings.