Background: Long non-coding RNAs (lncRNAs) are importantly involved in the initiation and progression of non- small cell lung cancer (NSCLC). However, the classification and mechanisms of lncRNAs remain largely elusive. Aim: Hence, we addressed this through bioinformatics analysis. Methods and results: We utilized microarray technology to analyze lncRNAs and mRNAs in twenty paired NSCLC tumor tissues and adjacent normal tissues. Gene set enrichment analysis, Kyoto Encyclopedia of Genes and Genomes, and Gene Ontology were conducted to discern the biological functions of identified differentially expressed transcripts. Additionally, networks of lncRNA-mRNA co-expression, including cis-regulation, lncRNAtranscription factor (TF)-mRNA, trans-regulation, and lncRNA-miRNA-mRNA interactions were explored. Furthermore, the study examined differentially expressed transcripts and their prognostic values in a large RNAseq dataset of 1016 NSCLC tumors and normal tissues extracted from the Cancer Genome Atlas (TCGA). The analysis revealed 391 lncRNAs and 344 mRNAs with differential expression in NSCLC tumor tissues compared to adjacent normal tissues. Subsequently, 43,557 co-expressed lncRNA-mRNA pairs were identified, including 27 lncRNA-mRNA pairs in cis, 9 lncRNA-TF-mRNA networks, 34 lncRNA-mRNA pairs in trans, and 8701 lncRNAmiRNA-mRNA competing endogenous RNA (ceRNA) networks. Notably, these lncRNAs were found to be involved in immune-related pathways. Six significant transcripts, including NTF4, PTPRD-AS, ITGA11, HID1AS1, RASGRF2-AS1, and TBX2-AS1, were identified within the ceRNA network and trans-regulation. Conclusion: This study brings important insights into the regulatory roles of lncRNAs in NSCLC, providing a fresh perspective on lncRNA research in tumor biology.