Metabolic dysregulation is one of the most common and recognizable features of cancer. Triosephosphate isomerase 1 (TPI1), which catalyzes the interconversion of dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde-3-phosphate (G3P) during giycosis and gluconeogenesis, is a crucial enzyme in the carbohydrate metabolism. However, the biological function and mechanism of TPI1 in cancer remain largely unknown. In this study, we have found that TPI1 expression was greatly decreased in clinical HCC samples, positively correlated with overall survival, and negatively associated with histological differentiation, tumor size and organ metastasis. Forced expression of TPI1 in HCC cells inhibited cell growth, migration, and invasion in vitro. Consistently, knockdown of TPI1 by shRNA promoted cell growth, migration and invasion. Moreover, overexpression of TPI1 led to slowed tumor growth and decreased tumor weight in vivo. Furthermore, cell cycle arrest was induced by TPI1 over expression. These phenotypes were associated with altered expression of beta-catenin, Vimentin, P53, P27 and CyclinD1. Therefore, our data suggested that TPI1 functioned as a tumor suppressor in HCC and might serve as a potential therapeutic target for the treatment of HCC. (C) 2016 Elsevier Inc. All rights reserved.