Objective To establish the expression profiles of differentially expressed miRNA and mRNA in oral squamous cell carcinoma (OSCC) and to investigate the roles of miRNA and mRNA associated with the occurrence and development of OSCC. Methods The expression profiles of miRNA and mRNA were constructed using a new generation of high-throughput sequencing techniques. The miRNA and mRNA associated with the occurrence and development of OSCC were predicted by Gene Ontology enrichment analysis and KEGG pathway analysis. Results We successfully constructed the differentially expressed miRNA and mRNA profiles of Chinese hamster buccal pouch squamous cell carcinoma. 11 known and 3 novel significantly differentially expressed miRNAs and 194 differentially expressed mRNAs were found. A miRNA can regulate multiple mRNAs, and multiple miRNAs can control one mRNA. Conclusions Differential expression of miRNA play a an important role in the carcinogenesis and development of OSCC through regulating mRNA and forming a complex regulatory network. It provides theoretical data for the occurrence, pathogenesis, clinical treatment and prognosis of OSCC.