Osteosarcoma (OS) is a common malignant bone cancer threatening children and young adults. Emerging evidence indicates that long non-coding RNAs (lncRNAs) play crucial roles in the progression of OS. Herein, we want to clarify the roles of lncRNA human leukocyte antigen complex group 11 (HCG11) in OS. Our data revealed that HCG11 expression is decreased in OS, which is a result of transcriptional repression of YY1. Low HCG11 level is closely associated with larger tumor size and shorter overall survival of OS patients. HCG11 negatively regulates cell proliferation, cell cycle, DNA replication in vitro and tumor growth in vivo. HCG11 can raise p27 Kip1 expression via binding to miR-942-5p and IGF2BP2, and p27 Kip1 acts as a key effector for HCG11 exerting biological functions. In conclusion, HCG11 is downregulated in OS, and restrains OS growth both in vitro and in vivo by raising p27 Kip1 expression via binding to miR-942-5p and IGF2BP2.