Endometrial cancer (EC) is the most common gynecologic malignancy, but the molecular events involved in the development and progression of EC remain unclear. Certain microRNAs (miRNAs) and DICER1 play important roles in cell motility and survival. This study investigated the role of miR-130b and DICER1 in EC. We profiled miR-130b and DICER1 expression in clinical samples explored its relationship with clinical parameters. A luciferase reporter assay assessed the miR-130b targeting potential of DICER1. We show both in vitro and in vivo that miR-130b overexpression along with DICER1 dysfunction leads to tumor aggression and miRNA synthesis abnormalities that are related to cancer hallmarks through DICER1-miRNAs axis modulation. We also identify the mechanism related to this potential tumor predisposing phenotype: miR-130b and loss of DICER1 induced abnormal expression of EMT-related genes, which constitutes a loop regulation of the miR-130b-DICER1-EMT axis.