Accumulated evidence revealed that numerous long noncoding RNAs (lncRNAs) have been found to be involved in the development and progression of hepatocellular carcinoma (HCC). LINC00628, a member of lncRNAs, has been reported to act as a tumor suppressor in gastric cancer and breast cancer. However, its potential role in HCC still remains unknown. Herein, we characterized the function of LINC00628 in HCC. Our investigation has revealed that LINC00628 were dramatically decreased in HCC tissues and cells, and inhibited the migration and invasion of HCC cells in vitro and in vivo. Moreover, LINC00628 exerted its tumor suppressive function by repressing the vascular endothelial growth factor A (VEGFA) promoter activity. A highly conserved region element in LINC00628 was identified by a cross-species comparative analysis, which is required for LINC00628 exerted its function. Dual-luciferase reporter assay showed that the conserved sequence mediated the interaction with a specific region of VEGFA promoter, resulting in a decrease of VEGFA expression. In conclusion, our results demonstrated that LINC00628 could function as a tumor suppressor in HCC via its conserved sequence elements interacting with a particular region of VEGFA promoter, suggesting that LINC00628 may serve as a novel promising target for diagnosis and therapy in HCC. © 2019 Wiley Periodicals, Inc.