Introduction: Oral Squamous Cell Carcinoma (OSCC) represents approximately 96% of the entire oral cancers. Epithelial-mesenchymal transition (EMT) is a factor contributing to the poor prognosis associated with OSCC. α-mangostin is one of the xanthones which show anti-cancer activities against some types of cancers and can suppress EMT-induced invasion by increasing E-cadherin expression. This study aimed to identify the viability of α-Mangostin to reduce the viable cells of HOC313. Methods: The role of α-mangostin to induce HOC313 cell culture at various concentrations which conducted on two groups: control group using only HOC313 cell line and intervention group comprising HOC313 cell line which added various concentrations. In this present study, cells were treated after reaching the confluency level of 80% in 5x103 cells/well. α-mangostin used had six concentrations: 1.25 µM, 2.5 µM, 3.75 µM, 5 µM, 6.25 µM, and 7.5 µM. Results: Concentration of α-mangostin had a significant effect on cell viability, p-value obtained was at 0.023 (p < 0.05). The Mann-Whitney test was also performed to identify significant differences in cell viability between control cells and all treatment cells were at 2.5 mg/ml and 5 mg/ml with the value p = 0.02 (p < 0.05). The concentrations α-mangostin at 1.25, 2.5, 3.75, 5, 6.25, and 7.5 µM is unable to reduce cell viability of HOC313. Conclusion: Low α-mangostin concentrations possibly result in a biphasic effect which leads to increase the viability cell of HOC313 cell line. Therefore, high α-mangostin concentrations might effectively inhibit cancer cell growth, migration, and invasion.