MicroRNAs (miRNAs) play an important role in the development and progression of endometrial carcinoma (EC). Recently, several studies have shown that microRNA-124 (miR-124) is downregulated in various cancers, which can affect tumor initiation and maintenance. However, the effects of miR-124 on EC are largely unknown. In this study, we identified the under-expression of miR-124 in 35 paired EC tissues and adjacent normal tissues. Further, functional experiments found that ectopic expression of miR-124 markedly suppressed cell proliferation, migration, and invasion of EC cells. It also induced cell apoptosis and G1-phase cell cycle arrest. Moreover, we identified signal transducer and activator of transcription 3 (STAT3) as a direct target of miR-124, and over expression of miR-124 not only induced changes in STAT3 expression but also altered expression of its target genes, cyclin D2 and matrix metalloproteinase 2, in the human endometrial carcinoma cell line HEC-1B. In addition to targeting STAT3 directly, we found that miR-124 suppresses phosphorylation of STAT3 through targeting IL-6R indirectly. Restored STAT3 expression through treatment with IL-6 cytokine partly abolished miR-124-mediated cell cycle arrest and apoptosis induction. These results combined with the tumorigenetic role of STAT3 in HEC-1B cells suggest that the antitumor effects of miR-124 are achieved, at least partly, through down regulation of STAT3 mRNA and its downstream target genes. Therefore, inhibition of constitutively activated STAT3 by ectopic expression of miR-124 in EC may provide a novel therapeutic strategy for the treatment of EC.