Increasing evidence has indicated the important roles of long noncoding RNAs (IncRNAs) in human osteosarcoma tumorigenesis. In present study, we aim to investigate the roles of IncRNA SNHG20 (small nucleolar RNA host gene 20) in osteosarcoma tumorigenesis and explore the in-depth molecular mechanism. Results showed that IncRNA SNHG20 expression was up-regulated in osteosarcoma samples and its high-expression indicated the poor prognosis. Loss-of-functional experiments indicated that SNHG20 knockdown inhibited the proliferation, invasion and induced the apoptosis of osteosarcoma cells in vitro. Specifically, SNHG20 knockdown up-regulated the expression levels of caspase-9, caspase-3 and Bax, indicating that SNHG20 knockdown accelerated the apoptosis of osteosarcoma cells via mitochondrial apoptosis pathway. Bioinformatics analysis revealed that miR-139 both targeted with the 3'-UTR of runt-related transcription factor 2 (RUNX2) and SNHG20, which was verified by luciferase reporter assay and RNA immunoprecipitation (RIP). In conclusion, our data reveals that IncRNA SNHG20/miR-139/RUNX2 axis modulates the osteosarcoma tumorigenesis and apoptosis via mitochondrial apoptosis pathway, providing a novel insight for the pathophysiological process. (C) 2018 Elsevier Inc. All rights reserved.