Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the oral cavity, which is mainly a series of atypical hyperplasia of oral epithelial cells, and the overall prognosis remains poor.GSE37991 and GSE38517 were downloaded from gene expression omnibus (GEO) to identify differentially expressed genes (DEGs). Functional enrichment analysis of DEGs was performed, weighted gene co-expression network analysis (WGCNA) was used. Protein-protein interaction (PPI) network was constructed. Core gene expression was visualized using a heatmap. Comparative toxicogenomics database (CTD) and miRNA analyses identified related diseases and regulatory miRNAs. Western blot (WB) was conducted to examine expression of COL11A1 and TGF-SMAD signaling components in OSCC samples.5163 DEGs were identified. DEGs were enriched in metabolic processes and signaling pathways, including TGF-β/SMAD and PI3K-Akt. WGCNA identified 11 core modules. PPI network analysis revealed five core genes: COL11A1, AURKA, MELK, CCNA2, and BUB1. Heatmap analysis showed that COL11A1 is highly expressed in OSCC. CTD analysis indicated that COL11A1 is associated with OSCC. miRNA prediction identified potential regulatory factors. Western blot analysis demonstrated that COL11A1 is overexpressed in OSCC and is associated with TGF-SMAD signaling, inflammation, and cell cycle progression.COL11A1 is highly expressed in OSCC and may serve as a target gene interacting with the TGF-SMAD signaling pathway.Copyright © 2024. Published by Elsevier Masson SAS.