Lung cancer is the most commonly occurring cancer attributed to the leading cause of cancer-related deaths globally. Non-small cell lung cancer (NSCLC) comprises 85% to 90% of lung cancers. The survival rate of patients with advanced stage NSCLC is in months. Moreover, the underlying molecular mechanisms still remain to be understood. We used 2 sets of microarray data in combination with various bioinformatic approaches to identify the differentially expressed genes (DEGs) in NSCLC patients. We identified a total of 419 DEGs using the Limma package. Gene set enrichment analysis demonstrated that “Citrate cycle (TCA cycle),” “RNA degradation,” and “Pyrimidine metabolism” pathways were significantly enriched in the NSCLC samples. Gene Ontology annotations of the 419 DEGs primarily comprised “glycosaminoglycan binding,” “cargo receptor activity,” and “organic acid binding.” Kyoto Encyclopedia of Genes and Genomes analysis revealed that DEGs were enriched in pathways related to “Malaria,” “Cell cycle,” and “IL-17 signaling pathway.” Protein protein interaction network analysis showed that the hub genes constituted of CDK1, CDC20, BUB1, BUB1B, TOP2A, CCNA2, KIF20A, CCNB1, KIF2C, and NUSAP1. Taken together, the identified hub genes and pathways will help understand NSCLC tumorigenesis and develop prognostic markers and therapeutic targets against NSCLC.