BACKGROUNDHepatocellular carcinoma (HCC) has become a great threat for people’s health. Many long noncoding RNAs are involved in the pathogenesis of HCC. SNHG15, as a tissue specific long noncoding RNAs, has been studied in many human cancers, except HCC.AIMTo explore the regulatory mechanism of SNHG15 in HCC.METHODSIn the present research, 101 HCC patient samples, two HCC cell lines and one normal liver cell line were used. RT-qPCR and Western blot analysis were applied to detect SNHG15, miR-490-3p and histone deacetylase 2 (HDAC2) expression. The regulatory mechanism of SNHG15 was investigated using CCK-8, Transwell and luciferase reporter assays.RESULTSOur research showed that up-regulation of SNHG15 was found in HCC and was related to aggressive behaviors in HCC patients. Moreover, knockdown of SNHG15 restrained HCC cell proliferation, migration and invasion. In addition, SNHG15 served as a molecular sponge for miR-490-3p. Further, miR-490-3p directly targets HDAC2. HDAC2 was involved in HCC progression by interacting with the SNHG15/miR-490-3p axis.CONCLUSIONIn conclusion, long noncoding RNA SNHG15 promotes HCC progression by mediating the miR-490-3p/HDAC2 axis in HCC.