OBJECTIVE To evaluate the effects of mouse embryonic palatal mesenchymal (MEPM) cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced. STUDY DESIGN An experimental study at Xinxiang Medical University. METHODS Primary MEPM cells were derived from palatal tissue on 30 pregnant C57BL/6 female mice (embryonic day13, GD13). The MEPM cells were placed in a humidified incubator at 37°C with 5% CO2 atmosphere with media replaced every other day. The third passage cells were seeded, and one part of cells were treated with 10nM TCDD (TCDD group). And others were treated with DMSO (≤0.05%, as control group). After 72h, MTT assay was analysed cell viability. Scratch wound-healing was analysed cell motility. Flow cytometry was analysed cell apoptosis and cycle. Western blot was analysed the expression of cyclinE, CDK2, P16 and P21. RESULTS TCDD inhibited the growth and migration of MEPM cells, while increased cell apoptosis. TCDD exposure inhibited the progression of cells from G1 to S phase and tended to reduce the number of cells entering the G2/M phase. TCDD inhibited expression of cyclinE and CDK2 at the protein level, instead increased the expression of P16 and p21 proteins. CONCLUSIONS TCDD might induce cleft palate by altering MEPM cells.