S100 calcium binding protein A7 (S100A7) has been proofed to play a carcinogenic role in several cancers. However, its role and the regulatory mechanism in Endometrial carcinoma (EC) was unknown. Western blot was applied to determine the expression of S100A7 and Mitogen-activated protein kinase (MAPK) pathway-related protein in EC cells. Functional in vitro experiments were conducted to explore the effects of S100A7 on cell proliferation, apoptosis, migration, invasion and angiogenesis in EC. As a result, S100A7 expression was dramatically up-regulated in EC cells. Overexpression of S100A7 enhanced EC cells proliferation, migration, invasion and angiogenesis, and suppressed cell apoptosis, as well as activated MAPK signaling pathway. Whereas, knockdown of S100A7 exerted the opposite effects. Our finding suggested that S100A7 may promote the malignant progression of EC by activating MAPK pathway, implying S100A7 has significant potential to be used as an emerging therapeutic target for EC treatment.