Objective: To investigate the effect of calcium sensitive receptor (CaSR) on epithelial mesenchymal transformation (EMT) of endometrial cancer cells in hypoxic environment. Methods: The Ishikawa cells of endometrial carcinoma were transfected with corresponding adenovirus respectively to form a blank group, a no-load group, a silent CaSR group and an overexpressed CaSR group. The change of cytoskeleton in different groups was observed by immunofluorescence assay after hypoxia. Expression of E-cadherin, Vimentin and CaSR were detected by Western bloting and immunofluorescence. Fluorescence dye fura-2/AM tracer was used to monitor the change of intracellular calcium ion concentration. Transwell assay was used to detect change in the ability of cell invasion and migration. Results: After hypoxia, the cytoskeleton of endometrial cancer cells changed like a spindle. Meanwhile, the expression of E-cadherin decreased, while the expression of Vimentin and CaSR increased. Endometrial cancer cells transfected with silencing and overexpressed CaSR adenovirus reduced and increased intracellular calcium flow respectively, which was negatively correlated with the expression of Vimentin and the ability of cell invasion and migration. Conclusion: The expression of EMT and CaSR in endometrial cancer cells increases after hypoxia, and the increased expression of CaSR inhibites the occurrence of EMT, which may be related to the regulation of cellular calcium ions.