Previous studies have shown that dietary calcium suppresses oral carcinogenesis, but the mechanism is unclear. p120‐catenin (p120) is a cytoplasmic protein closely associated with E‐cadherin to form the E‐cadherin–β‐catenin complex and may function as a tumor suppressor in the oral epithelium. To determine whether p120 is involved in the mechanism by which dietary calcium suppresses oral carcinogenesis, The normal, low, or high calcium diet was fed control mice (designated as floxed p120 mice) or mice in which p120 was specifically deleted in the oral squamous epithelium during the adult stage (designated as p120cKO mice). All mice were exposed to a low dose of oral cancer carcinogen 4‐nitroquinoline 1‐oxide and rates of oral squamous cell carcinoma (OSCC) and proliferation and differentiation in the cancerous and non‐cancerous oral epithelium of these mice were examined. The results showed that the low calcium diet increased rates of OSCC and proliferation of the non‐cancerous oral epithelium and decreased differentiation of the non‐cancerous oral epithelium, but had no effect on cancerous oral epithelium. In contrast, the high calcium diet had opposite effects. However, the effect of the dietary calcium on the rates of OSCC, proliferation, and differentiation of the non‐cancerous epithelium were not seen in p120cKO mice. Based on these results, we conclude that p120 is required for dietary calcium suppression of oral carcinogenesis and oral epithelial proliferation and dietary calcium induction of oral epithelial differentiation. J. Cell. Physiol. 232: 1360–1367, 2017. © 2016 Wiley Periodicals, Inc. The aim of the present study was to determine whether p120‐catenin plays a role in dietary calcium‐induced oral carcinogenesis. The results showed that knockout of p120‐catenin blocked the inhibitory effect of dietary calcium on tumor rates and proliferation and the stimulatory effect of dietary calcium on tumor differentiation in the oral epithelium. These data suggest that p120‐catenin plays a critical role in dietary calcium‐suppressed carcinogenesis and dietary calcium regulation of proliferation, differentiation. Our findings illustrate a mechanism by which dietary calcium suppresses oral carcinogenesis will help in the development of better preventive and therapeutic strategies for oral cancers.