Background: Previous studies have suggested that long non-coding RNAs (lncRNAs) were involved in tumorigenesis of various human carcinomas, including osteosarcoma (OS). However, the expression and specific role of lncRNA HLA complex group 11 (HCG11) in OS remain unknown. The current study aimed at revealing the role of lncRNA HCG11 and its related mechanism in OS. Methods: lncRNA HCG11 expression was verified with RT-qPCR followed by sublocalization determination. LncRNA-microRNA (miRNA) and miRNA-mRNA interactions were predicted by online bioinformatics websites. Validation was performed using dualluciferase reporter gene assays, and gain-and loss-of-function experiments. The effects of lncRNA HCG11, miR-579 and matrix metalloproteinase 13 (MMP13) on the proliferation, migration and invasion, epithelial-mesenchymal transition (EMT) of OS cells were detected using cell counting kit-8 (CCK-8), Transwell assays and Western blot analysis. Results: LncRNA HCG11 overexpression was observed in OS tissues and cell lines. Downregulation of lncRNA HCG11/MMP13 or overexpression of miR-579 blocked the progression of OS cells. LncRNA HCG11, which is located in the cytoplasm, promoted MMP13 expression through sponging miR-579. Conclusion: LncRNA HCG11 might be beneficial for OS aggravation via sponging miR-579 and facilitating MMP13 expression, which represents a candidate biomarker and target for OS therapy.