Accumulating evidence has demonstrated that microRNAs (miRNAs) play critical roles in cancer initiation and development by functioning either as oncogenes or as tumor suppressors. The role of microRNA-449a (miR-449a) in endometrial cancer remains unclear. We examined the levels of miR-449a and miR-449b in benign endometrium, type I and type II endometrial cancer tissues by quantitative real-time polymerase chain reaction. To further investigate the roles of miR-449a in regulating the behavior of endometrial cancer cells, we overexpressed miR-449a in the endometrial cancer cell line HEC-1B, which had low endogenous miR-449a expression. We analyzed the effects of miR-449a overexpression on CDC25 expression, proliferation, invasion and apoptosis of HEC-1B cells. We found that miR-449a and miR-449b levels were markedly reduced in type II endometrial cancer tissues but not in type I endometrial cancer tissues compared with normal endometrium. Overexpression of miR-449a significantly inhibited the proliferation, invasion and clonogenic survival of HEC-1B cells. MiR-449a overexpression also induced apoptosis in HEC-1B cells. In addition, real-time RT-PCR and western blot analysis showed that CDC25A expression was suppressed by miR-449a overexpression. Our results suggest that miR-449a may act as a tumor suppressor by targeting CDC25A in endometrial cancer.