OBJECTIVE: To investigate the role of miR-5692a in hepatocellular carcinoma (HCC), and to further study the relationship between miR-5692a expression and clinical pathology as well as the prognosis of HCC. PATIENTS AND METHODS: The expression level of miR-5692a in 96 pairs of HCC tissues and para-cancerous tissues were detected by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The relationship between miR-5692a and pathological indicators as well as the prognosis of HCC was analyzed by Kaplan-Meier curves. For in vitro experiments, qRT-PCR was used to detect the expression of miR-5692a in HCC cell lines. Furthermore, small interference sequence of miR-5692a was constructed. Cellular functions of HCC cells after miR-5692a knockdown were detected by cell counting kit-8 (CCK-8), colony formation and transwell assay, respectively. The underlying mechanism of miR-5692a in regulating the development of HCC was detected by Western blot. RESULTS: MiR-5692a was overexpressed in HCC tissues than that of para-cancerous tissues. HCC patients with higher miR-5692a expression exhibited a higher prevalence of lymph node metastasis and distant metastasis, as well as lower overall survival than those patients with lower level of miR-5692a expression. In vitro experiments demonstrated that miR-5692a knockdown resulted in decreased proliferation and invasion, and increased apoptosis of HCC cells. Western blot results revealed that EMT-related (epithelial-mesenchymal transition) genes, including N-cadherin, Vimentin, ß-catenin and MMP9, were downregulated after miR-5692a knockdown. Rescue experiments indicated that miR-5692a promoted malignant progression of HCC via regulating MMP9. CONCLUSIONS: MiR-5692a was overexpressed in HCC patients, which was remarkably correlated with HCC stage, distant metastasis and poor prognosis. In addition, miR-5692a promoted the malignant progression of HCC via regulating MMP9.