Cancer cells frequently employ metabolic adaptations to sustain proliferation in challenging microenvironments. Recent research has shed light on the significance of lipid metabolism in cancer progression. Heightened rates of de novo fatty acid synthesis or increased uptake of fatty acids are frequently observed in cancer cells. However, the role of lipid catabolism, specifically the breakdown of lipids stored in lipid droplets, in cancer remains relatively understudied. Our study focuses on the involvement of adipose triglyceride lipase (ATGL) and monoglyceride lipase (MGL) in lung cancer. ATGL is responsible for initiating triglyceride breakdown, and its potential role in lung cancer development has been suggested, considering the observed accumulation of lipid droplets in solid tumours. MGL, another key lipase involved in intracellular lipid degradation, has been shown to impact signalling pathways and influence cancer pathogenesis. Through genetic manipulation of lipid hydrolases in a panel of non-small cell lung cancer (NSCLC) cell lines we aim to explore the role of these enzymes in cellular metabolism. Our preliminary findings indicate that deletion of either ATGL or MGL in some but not all NSCLC cell lines results in increased proliferation and metabolic changes. Our primary objective is to unravel the intricate interplay between lipid hydrolysis enzymes, lung cancer cell metabolism, and proliferation. By gaining a deeper understanding of these mechanisms, we aim to shed light on the factors driving lung cancer progression and identify new dependencies of lung cancer cells. This knowledge holds the potential to unlock novel avenues for targeted therapies and personalized treatment strategies.