Human pancreatic cancer is one of the most aggressive types of cancer, with a high mortality rate. Due to the high tolerance of such cancer cells to nutrient starvation conditions, they can survive in a hypovascular tumor microenvironment. In this study, the dichloromethane extract of the roots of <i>Ferula hezarlalehzarica</i> showed potent preferential cytotoxic activity with a PC<sub>50</sub> value of 0.78 μg/mL. Phytochemical investigation of this extract led to the isolation of 18 compounds, including one new sesquiterpenoid (<b>6</b>) and one new monoterpenoid (<b>18</b>). All isolated compounds were evaluated for their preferential cytotoxicity against PANC-1 human pancreatic cancer cells by employing an antiausterity strategy. Among them, ferutinin (<b>2</b>) was identified as the most active compound, with a PC<sub>50</sub> value of 0.72 μM. In addition, the real-time effect of ferutinin (<b>2</b>) and compound <b>6</b> against PANC-1 cells, exposed to a nutrient-deprived medium (NDM), showed cell shrinkage, leading to cancer cell death within a short period of exposure. Compounds <b>2</b> and <b>6</b> also inhibited colony formation of PANC-1 cells. The present study indicates that the dichloromethane extract of the roots of <i>F. hezarlalehzarica</i> is a rich source of bioactive compounds for targeting PANC-1 cells.