The dysregulated expression of LSINCT5 (long stress-induced non-coding transcript 5) has been found in various human tumors, and was generally related to cancer progression and unfavorable prognosis. Although the role of LSINCT5 in osteosarcoma was reported not long ago, the sample size of that study was limited. Our study presented more evidence about the clinical significance and biological function of LSINCT5 in osteosarcoma. In our results, we found LSINCT5 expression was increased in osteosarcoma tissue samples and cell lines, and high LSINCT5 expression was associated with advanced Enneking stage, large tumor size, high histological grade and present distant metastasis. Meanwhile, we observed high LSINCT5 expression was correlated with worse overall survival, and high LSINCT5 expression could be an independent poor predictor for overall survival in osteosarcoma cases. Moreover, we found inhibition of LSINCT5 expression suppressed cell proliferation, migration and invasion in vitro, and LSINCT5 overexpression dramatically facilitated cell proliferation, migration and invasion in vitro. In conclusion, our study suggests that LSINCT5 exerts oncogenic function in osteosarcoma cells, and may be a potential predictor for clinical outcome in osteosarcoma patients.