Purpose: This article reports on FLVCR-AS1 effects on osteosarcoma (OS) growth. Methods: Tumor tissue and adjacent normal tissue of 48 OS patients were collected. HOS and 143B cells were transfected. Gene expression was examined with qRT-PCR and Western blot. CCK8 assays and cell cloning was performed to measure cell proliferation. Cell cycle and apoptosis were assessed. Luciferase-reporter gene assays and RNA pull-down tests were used to detect targeting relationships between genes. Results: Prominently higher FLVCR-AS1 expression was found in OS tissue and cells, and was associated with poor prognosis (P<0.05, P<0.01, or P<0.001). Compared with the siCtrl group, 143B and HOS cells of the siFLVCR-AS1 group had significantly lower OD450 values and clone numbers and obviously higher percentages of cells in the G1 phase and apoptosis (P<0.01 or P<0.001). miR381-3p expression was directly inhibited by FLVCR-AS1, and CCND1 expression was directly suppressed by miR381-3p. Compared with the FLVCR-AS1 group, 143B cells of the FLVCR-AS1+ miR381-3p mimic group and FLVCR-AS1+ siCCND1 group showed remarkably lower OD450 values and clone numbers obviously higher apoptosis and percentage of cells in the G1 phase (P<0.05, P<0.01, or P<0.001). Conclusion: FLVCR-AS1 promoted OS growth by upregulating CCND1 expression via downregulation of miR381-3p. © 2020 Yang et al.