The functional characterization of non-coding microRNAs (miRNAs) has been shown to be associated with the pathophysiology of the disease, but it is still a challenging task to elucidate the pathogenesis of microRNAs and disease. In addition, the understanding of the role of miRNAs in the development of LSCC still needs further exploration. In this study, to identify miRNAs that play a key role in LSCC, we analyzed miRNA and mRNA sequence data from 162 LSCC samples from the TCGA database, and screened specific miRNAs and mRNAs by differential gene expression analysis. And then, construct a differentially expressed miRNAs and mRNAs interaction network. In our investigation, 23 miRNAs (P < 0.01, log2FoldChange > 2) and 331 mRNAs (P < 0.01, log2FoldChange > 4) were identified differentially expressed in LSCC and reduced the number of loosely linked miRNAs and mRNAs according to appropriate thresholds. Finally, 13 miRNAs and 35 mRNAs were enriched in a network. Our study provides the most comprehensive information on the expression of miRNAs in LSCC and identifies the known oncogenic miRNAs (such as miR-163a), as well as aberrant expression of novel miRNAs involved in cell regulation and metabolic defects that occur during development of LSCC.