Endometrial cancer (EC) is the most common gynecological tumor in developed countries with an increasing incidence. Left‑right determination factor 2 (LEFTY2), a suppressor of cell proliferation and tumor growth, is a negative regulator of EC progression. The roles of LEFTY2 are emerging; however, the regulatory mechanisms of its expression have not been well understood. MicroRNA (miR)‑215 as an oncogene serves an important role in tumorigenesis by regulating target genes. In the present study, it was demonstrated that overexpression of miR‑215 promoted epithelial to mesenchymal transition (EMT), colony formation and DNA synthesis in EC HEC‑1A cells and its expression was upregulated in EC tissues. Using online miR target prediction software, it was revealed that LEFTY2 is predicted as a target of miR‑215. Using western blot analysis and immunofluorescence assays, it was demonstrated that overexpression of miR‑215 markedly downregulated LEFTY2 protein expression levels in HEC‑1A cells and LEFTY2 protein expression was downregulated in EC tissues, which was inversely correlated with miR‑215 expression. Furthermore, the present study indicated that overexpression of LEFTY2 protein promoted mesenchymal to epithelial transition and sensitized HEC‑1A cells to cisplatin treatment. In addition, it was revealed that the overexpression of LEFTY2 inhibited colony formation and DNA synthesis in HEC‑1A cells. Thus, miR‑215 may promote EMT and proliferation by regulating LEFTY2 in EC.