In this study, we found that expression of miR-454-3p increased after HOTAIR knockdown, and we found that HOTAIR recruited EZH2 and DNMT1 to the promoter of miR-454-3p, increased DNA methylation at the miR-454-3p promoter regions and repressed miR-454-3p expression in chondrosarcoma. Here, HOTAIR is linked to chondrosarcoma.