Osteosarcoma (OS) is a malignant bone tumor of mesenchymal origin, which is common in children and adolescents. Long non-coding RNA (lncRNA) SNHG11 plays important regulatory roles in various cancers, particularly in promoting cell migration, invasion, and proliferation. However, the function and regulatory mechanisms of SNHG11 in osteosarcoma remain unclear. In this study, we found that overexpression of SNHG11 in human osteosarcoma U2OS cells significantly inhibited cell proliferation and promoted apoptosis. Overexpression of SNHG11 in U2OS cells resulted in significant differential expression of 344 genes, including 82 upregulated genes and 262 downregulated genes. The upregulated genes were not significantly enriched in GO-P, although HMGCS2 and IL24 may play important roles. The downregulated genes were significantly enriched in GO-P related to cell adhesion and migration, with key genes including KRT17, CXCL14, TRIB2, COL5A1, CCL24, SOX2, and COL6A3.SNHG11 may interact with KRT6B, SERPINB12, and DCD proteins to regulate downstream targets. ChIRP-seq (RNA) sequencing revealed that SNHG11 specifically binds to EEF2, RPS4X, and ACTG1. ChIRP-seq (DNA) sequencing showed that SNHG11 gene was mainly enriched in biological processes such as negative regulation of apoptosis. Integrated analysis of ChIRP-seq (RNA) revealed 32 overlapping genes, suggesting that SNHG11 may contribute to osteosarcoma progression by binding to DCD and regulating these targets. Similarly, ChIRP-seq (DNA) analysis identified 16 overlapping genes. Combined with protein profiling data, we speculate that SNHG11 may be involved in osteosarcoma progression by binding to SERPINB12 and regulating transcription. In conclusion, lncRNA SNHG11 plays a critical role in osteosarcoma development by regulating cellular information carriers at the DNA, RNA, and protein levels.