lncRNA–mRNA co-expression pairs and prognostic markers related to the development of laryngeal squamous cell carcinoma (LSCC) were investigated. The lncRNA and mRNA expression data of LSCC in GSE84957 and RNA-seq data of 112 LSCC samples from TCGA database were used. Differentially expressed genes (DEGs) and lncRNAs (DE-lncRNAs) between LSCC and para-cancer tissues were identified. Co-expression analysis of DEGs and DE-lncRNA was conducted. Protein–protein interaction network for co-expressed DEGs of top 25 DE-lncRNA was constructed, followed by survival analysis for key nodes in co-expression network. Finally, expressions of several DE-lncRNAs and DEGs were verified using qRT-PCR. The lncRNA–mRNA network showed that ANKRD20A5P, C21orf15, CYP4F35P, LOC_I2_011146, XLOC_006053, XLOC_I2_003881, and LOC100506027 were highlighted in network. Some DEGs, including FUT7, PADI1, PPL, ARHGAP40, MUC21, and CEACAM1, were co-expressed with above lncRNAs. Survival analysis showed that PLOD1, GLT25D1, and KIF22 were significantly associated with prognosis. qRT-PCR results showed that the expressions of MUC21, CEACAM1, FUT7, PADI1, PPL, ARHGAP40, ANKRD20A5P, C21orf15, CYP4F35P, XLOC_I2_003881, LOC_I2_011146, and XLOC_006053 were downregulated, whereas the expression of LOC100506027 was upregulated in LSCC tissues. PLOD1, GLT25D1, and KIF22 may be potential prognostic markers in the development of LSCC. C21orf15-MUC21/CEACAM1/FUT7/PADI1/PPL/ARHGAP40 are potential lncRNA–mRNA pairs that play significant roles in the development of LSCC. Graphical abstract Several genes, PLOD1, GLT25D1, and KIF22, are identified as potential prognostic markers for LSCC development. In addition, lncRNA–mRNA pairs related to LSCC were explored, and 6 DEGs (MUC21, CEACAM1, FUT7, PADI1, PPL, and ARHGAP40) and 7 DE-lncRNAs (ANKRD20A5P, C21orf15, CYP4F35P, XLOC_I2_003881, XLOC_I2_011146, XLOC_006053, and LOC100506027) were validated to be abnormally expressed in LSCC tissue.