Hepatocellular carcinoma (HCC) is one of the most common cancer in the world and the main cause of cancer death. Chronic hepatitis B virus (HBV) infection is the major cause of HCC. HBx, as a transactivator, plays an important role in the occurrence and development process of HCC leading by HBV infection. XTP8, related to HBx, however, there are no studies on the function of XTP8 in HCC. In our research, we demonstrated that XTP8 was significantly up-regulated in HCC tissues compared with non-cancerous tissues in Oncomine, TCGA and GEO database. Moreover, Kaplan-Meier Plotter analysis indicated that patients with higher XTP8 expression had significantly lower overall survival. Our immunohistochemical results suggested that XTP8 protein expression in HCC tissues was dramatically higher compared with control normal tissues. In vivo xenograft experiments on nude mice, the overexpression of XTP8 promoted the tumorigenic ability of HepG2 cells. In HepG2 and Huh7 cells, XTP8 upregulated FOXM1 expression to promote cell proliferation and inhibited cell apoptosis. FOXM1 knockdown reduced promoter activity of XTP8 to downregulate XTP8 expression. Thiostrepton, an inhibitor of FOXM1, decreased XTP8 expression. Therefore, our study demonstrates that XTP8 is a valuable prognostic predictor for HCC and there is a novel positive regulatory feedback loop between XTP8 and FOXM1 promoting the development of HCC. (C) 2019 Published by Elsevier Inc.