Objective To explore the effect of long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) expression on the proliferation and pathology of osteosarcoma implanted subcutaneously in nude mice. Methods The osteosarcoma U2OS cell line with stable low expression of MALAT-1 was constructed by lentivirus infection, and the expression of MALAT-1 was verified by quantitative real-time polymerase chain reaction (qPCR). Twelve male nude mice aged 4-6 weeks were randomly divided into experimental group and control group. Osteosarcoma U2OS cells with stable low expression of MALAT-1 were implanted subcutaneously in the experimental group, while osteosarcoma U2OS cells infected by empty lentivirus were implanted subcutaneously in the control group. The volumes of subcutaneous osteosarcoma were measured and recorded on the 3^rd, 6^th, 9^th, 12^th, 15^th, 18^th and 21^st days after implantation. On the 21^st day after tumor transplantation, the nude mice were sacrificed. The osteosarcoma was taken out completely and weighed. The microscopic morphology of the osteosarcoma tissue was observed with hematoxylin-eosin (H-E) staining, and the expression levels of proliferacting cell nuclear antigen (PCNA) and vascular endothelial growth factor (VEGF) were detected by immunohistochemistry. Results Compared with the control group, the tumors in the experimental group grew slower and had smaller volume and weight on the 21^st day after implantation (both P<0.01). H-E staining showed that there was increased matrix composition and decreased cell density in the tumors of the experimental group. Immunohistochemistry showed that PCNA expression was decreased in the tumors of the experimental group (P<0.05). In the experimental group, the median integral optical density (IOD) of PCNA positive staining was 8 531.03, and the expression rate of positive cells was 29.3% (1 758/6 000). In the control group, the median IOD was 27 548.23, and the positive cell expression rate was 56.5% (3 392/6 000). There was no significant difference in the expression of VEGF between the experimental group and the control group (P>0.05). In the experimental group, the IOD of VEGF positive staining was 18 179.490±18 299.433, and the expression rate of positive cells was 51.0% (3 063/6 000). In the control group, the IOD was 15 850.632±9 341.063, and the positive cell expression rate was 50.0% (3 001/6 000). Conclusion Inhibiting the expression of MALAT-1 in osteosarcoma can slow down tumor growth, reduce tumor invasiveness, and promote tumor cell necrosis in solid tumors.