Genes involved in lipid metabolism have been considered potential therapeutic targets in lung cancer because lipid metabolism is severely disrupted in this cancer. Monoglyceride lipase (MGLL) is a lipolytic enzyme that converts monoacylglycerides to fatty acids and glycerol. MicroRNAs (miRNA), one of the most important epigenetic regulators of gene expression, are also considered potential biomarkers in diagnosing, treating, and prognosis lung cancer. This study aimed to investigate the potential effects of MGLL and related miRNAs (miR-302b-5p, miR-190a-3p, miR-450a-2-3p) in the pathogenesis of non-small cell lung cancer (NSCLC) by examining their expression levels and regulatory mechanisms. We analysed the expression levels of MGLL and miRNAs in 30 NSCLC and 20 non-cancerous tissues by qPCR. We performed in silico analyses to determine the biological functions of MGLL and miRNAs in NSCLC. A protein-protein interaction (PPI) network was constructed for MGLL, and gene ontology (GO) analysis, and the interacting genes were analysed using the TCGAnalyzer tool. Our study showed that the expression levels of MGLL, miR-302b-5p, miR-190a-3p and miR-450a-2-3p were significantly decreased in NSCLC tissues (p < 0.05). Also, according to TCGAnalyzer, MSRB3, HTR4, and FCER1G genes were downregulated genes for NSCLC. We showed that miR-302b-5p, miR-190a-3p, and miR-450a-2-3p significantly regulate the TGF-β signalling pathway. In conclusion, this study provides evidence for the potential role of MGLL and microRNAs (miR-302b-5p, miR-190a-3p, miR-450a-2-3p) in NSCLC. In subsequent studies, it was determined that MSRB3, FCER1G and LTB4R2 genes, especially the HTR4 gene, could be potential target genes for lung cancer.