Recent studies suggest important roles for long noncoding RNAs as essential regulators of human cancer. GClnc1 was found to be upregulated in gastric cancer, playing oncogenic roles. However, the biological function and underlying mechanism of GClnc1 in osteosarcoma (OS) remain unclear. Here, we report that GClnc1 is upregulated in OS tissues and its high expression predicts poor prognosis of patients. Functional analyses show that overexpression of GClnc1 promotes OS cells growth; whereas knockdown of GClnc1 has completely opposite effects. Consistently, overexpression of GClnc1 promotes tumorigenicity of OS cells in vivo. Mechanistically, GClnc1 directly binds to p53 and blocks the binding of p53 to acetyltransferase p300, and thereby suppresses acetylation of p53, leading to the reduced expression of p21 and BAX. This study shed light on the oncogene role of lncRNA GClnc1, a new modulator of p53 signaling, in OS. (C) 2018 Published by Elsevier Inc.