The anticancer activity of Peucedanum praeruptorum Dunn extract (PPDE) was investigated in vitro in the HepG2 human hepatoma cell line and compared to normal human liver cells (L02 cells). The effect of the PPDE on the proliferation of the cells was measured by MTT assays, and the levels of enzymes and small molecules implicated in oxidative stress regulation were measured using specific reagent kits. The expression levels of genes implicated in apoptosis (Bax, Bcl-2, caspase-3, caspase-8, and caspase-9) and oxidative stress (SOD1 and SOD2) were quantified by RT-qPCR. Lastly, HPLC was employed to analyze the composition of the PPDE. PPDE was found to significantly inhibit the proliferation of HepG2 cells but had little effect on the proliferation of normal liver cells. PPDE increased the levels of reactive oxygen species and malonaldehyde, a lipid peroxidation product, in HepG2 cells, and it reduced the activities of antioxidant enzymes, as well as the levels of γ-GCS and reduced glutathione (GSH), suggesting that it inhibited the ability of cancer cells to regulate intracellular oxidative stress. PPDE also increased the expression of the genes encoding Bax, caspase-3, caspase-8, and caspase-9 and decreased the expression of Bcl-2, SOD1, and SOD2 in HepG2 cells, suggesting that PPDE induced the apoptosis of the liver cancer cells. HPLC analysis identified that the components of PPDE included caffeic acid, isochlorogenic acid C, myricetin, baicalin, luteolin, and kaempferol, all of which have demonstrated antioxidant properties.