2-(Cyclohexylmethyl)-Plumbagin, a naphthoquinone derivative, exhibits selective cytotoxicity towards PANC-1 human pancreatic cancer cells under nutrient-deprived conditions—a situation akin to the pancreatic cancer tumor microenvironment—over those in nutrient-rich settings, with PC50 values of 0.11 and 47.2 µM, respectively. At a 1 µM concentration, it triggers apoptosis in PANC-1 cells. Furthermore, this compound specifically inhibits the phosphorylation of Akt and mammalian target of rapamycin (mTOR) in PANC-1 cells under nutrient scarcity. In a MiaPaCa-2 pancreatic cancer mouse xenograft model, it significantly reduces tumor volume and weight when administered at 50 and 250 µg/animal dosages five times weekly.