Luteolin is a flavonoid and considered to be important for anti-cancer activity against many cancer cells. However its mechanism of action is poorly understood as well as systematics study on its action on different cancer cell line is still obscure. In this study we checked luteolin activity against number of cell line and according to our screen mouse liver cancer cells (HepG2) is found to be most susceptible to its action. We have also measured how different concentrations of luteolin effects on cell proliferation of HepG2 over 48 h of window. Next we studied the underlying mechanism of luteolin action, and found its inducing apoptosis of HepG2 cell, apoptosis was monitored based on propidium iodide internalization assay using flow cytometer (FACS). Next we measured ROS generation ability and lipid peroxidation effect induced by luteolin and measured using TBARS assay. Further investigation revealed that luteolin is causing extensive DNA degradation in HepG2 cells. Finally Quantitative real time PCR analysis results showed that luteolin significantly up-regulated the expression of both intrinsic and extrinsic caspases as well as executioner caspases. It is notable that intrinsic caspase (Caspase-9) and executioner caspase (Caspase-3) were highly expressed when compared with the extrinsic caspase (Caspase-8). Altogether our result clearly showed the details mechanistic pathway by which luteolin is inducing apoptosis in HepG2. The promising anticancer potential of luteolin can be effectively utilized in future for anticancer drug development.