ABSTRACT: Galangin, a natural flavonoid, derived from honey and Alpinia officinarum Hance (Zingiberaceae) has excellent was anti-tumor and anti-inflammatory properties. w It has been extensively studied as a novel therapeutic agent forhich was widely used in the treatment of various cancers. However, the effect of galangin in HCC remains elusive. Using RNA sequencing, the differential expression of LncRNA in MHCC97H cells treated with galangin was investigated in the present study. Furthermore, the expression of H19 was also determined in MHCC97H cells following treatment with galangin. And the effect of knockdown and overexpression of H19 on cell apoptosis, cell cycle, migration and invasion of HCC cells was also evaluated. Moreover, the in vivo effect of galangin on tumor development was also determined in nude mice. This study identified aT total of 50 LncRNAs were to be significantly differentially expressed by RNA-seq analysis in MHCC97H cells treated with galangin. It has been demostreated that noncoding RNA H19 are abnormally expressed in different cancers. Our results showed that Besides, the expression of H19 was markedly reduced after following treatment with galangin treatment in MHCC97H cells. In addition, galangin could increase the occurrence of cell apoptosis. Moreover, compared to the Control group, the galangin-treated group inhibited cell migration and invasion in MHCC97H cells.To further investigated if H19 expression pattern affect cell apoptosis, migration and invasion, knock down and overexpression of H19 vector were constructed. The results of the knockdown of H19 expression showed knock down of H19 expression increased cell apoptosis and decreasedinhibited invasion. In addition, RNA-seq data showed also identified 161 mRNA which were was significantly differentially expressed after following treatment withof galangin. To further determine the underlying mechanism,confirmed cell apoptosis, p53 protein and its related proteins were was analyzed through micor RNA 675-3p (miR675-3p) which was in the H19 locus. Notably, Tthe results indicatedshowed that reduced knockdown of H19 and miR675 induced the protein expression of p53, eventually promoting cell apoptosis expression of H19 and miR675-3p increased p53 expression in MHCC97H cells. These results indicated that galangin promoted cell apoptosis through the regulation of H19 and miR675 expression in MHCC97H cells. Furthermorely, galangin was used to treated in nude mice. Tthe in vivo result showed that compared to the Control group, inhibited tumor growth was remarkably suppressed and reduced expression of H19 in galangin-treated group. Taken together, these results indicated that galangin regulated cell apoptosis which associate with p53 protein through H19 and miR675 expression in MHCC97H cells.Collectively, our data suggested that galangin plays a role in hepatocarcinogenesis through regulation of H19 expression pattern.