BACKGROUND: Tristetraprolin (TTP) can inhibit the abnormal proliferation of malignant tumors but there are no studies involving TTP and esophageal squamous cell carcinoma (ESCC). We aimed to determine the effect of TTP on ESCC cell proliferation and to elucidate the underlying mechanism. METHODS: The human ESCC cell line, KYSE-510, and the human ESCC cell line, KYSE-150, stably infected with tetracycline-inducible expression (Tet-on-TTP and Tet-on-EV, respectively) were screened with puromycin. After Tet-on-TTP KYSE-150 cells were treated with different concentrations of doxycycline [Dox] (0, 0.5, and 1 ug/mL), the levels of TTP mRNA and protein expression were detected by real-time fluorescent quantitative PCR and western blotting, respectively. The effects of TTP on proliferation and migration were estimated by CCK-8 and Transwell assays, respectively. Cell apoptosis and cell cycle were measured by flow cytometry. Cellular apoptosis-related gene protein expression was determined by western blotting. RESULTS: TTP overexpression significantly inhibited KYSE-510 and KYSE-150 proliferation. TTP overexpression also significantly inhibited KYSE-150 migration. In addition, TTP expression upregulation promoted the KYSE-150 apoptosis and induced cell cycle arrest in the G CONCLUSION: TTP inhibited ESCC cell proliferation, promoted ESCC cell apoptosis, and arrested cell cycle progression in the G