Objective To screen for differentially expressed long non-coding RNA (LncRNA) in oral squamouscell carcinoma tissue samples from Chinese hamsters and predict their target genes, and explore the biological functions and enrichment signaling pathways of these target genes. Methods The squamous cell carcinoma model was established inChinese hamsters by 9,10-dimethyl-1,2-benzanthracene smear method. The profile of differentially expressed LncRNA wasconstructed by high-throughput sequencing technology. Differentially expressed LncRNAs were screened by biosignaltechnology and target genes were predicted. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG)enrichment analyses were used to predict the biological function of differentially expressed genes and enriched signaling pathways, respectively. Results Compared with normal tissue samples, 54 differentially expressed LncRNAs werescreened from squamous cell carcinoma tissue samples, of which 31 were upregulated and 23 were downregulated.Functional analysis identified 73 GO entries associated with oral cancer, and 25 enriched KEGG signaling pathways.Conclusions Differentially expressed LncRNA in Chinese hamster oral squamous cell carcinoma samples likely play a rolein regulating various biological functions and oral cancer-related signaling pathways by targeting numerous genes, and may play an important role in the development of oral squamous cell carcinoma.