TCP1OL (T-complex 10 (mouse)-like) has been identified as a liver and testis-specific gene. Although a potential transcriptional suppression function of TCP1OL has been reported previously, biological function of this gene still remains largely elusive. In this study, we reported for the first time that TCP1OL was significantly down-regulated in clinical hepatocellular carcinoma (HCC) samples when compared to the corresponding non-tumorous liver tissues. Furthermore, TCP1OL expression was highly correlated with advanced cases exceeding the Milan criteria. Overexpression of TCP1OL in HCC cells suppressed colony formation, inhibited cell cycle progression through GO/G1 phase, and attenuated cell growth in vivo. Consistently, silencing of TCP1OL promoted cell cycle progression and cell growth. Therefore, our study has revealed a novel suppressor role of TCP1OL in HCC, by inhibiting proliferation of HCC cells, which may facilitate the diagnosis and molecular therapy in HCC. (c) 2014 Elsevier Inc. All rights reserved.