This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.Objectives: Mastic is a resinous extract from the stem and main leaves of Pistacia lentiscus, grown only in the Chios island of Greece. Mastic has antibacterial, anti-inflammatory, anticancer, and anti-ulcer activities. Although mastic has been widely studied, its inhibitory effect against cancer cells, especially oral cancer cells, has not been elucidated. The purpose of this study was to assess the anticancer effects of mastic on human oral cancer YD-10B cells. Methods: YD-10B cells were cultured in 0, 1, 2, 5, and 10 mg/mL mastic for 24 h. Cell count, viability, morphology, colony-forming assay, and DAPI staining were analyzed. Results: Mastic treatment of YD-10B cells resulted in a dose-dependent inhibition of cell growth, and almost all the cells in the 10 mg/mL culture were dead (P<0.05). Mastic treatment induced a morphological change and nuclear fragmentation in the YD-10B cells, and inhibited colony formation of YD-10B cells in a dose-dependent manner. Conclusions: These results indicate that mastic exhibited anticancer effects on the YD-10B cells through changes in cell morphology and apoptosis.