Esculetin (ESC), a coumarin derivative, has shown to possess antioxidant, anti-inflammatory, anticancer and chemopreventive properties. In the present study, we evaluated the chemopreventive activity of ESC against benzo[a]pyrene (B[a]P) induced lung carcinogenesis in Swiss albino mice by measuring antioxidant parameter, like lipid peroxidation, reduced glutathione (GSH) and superoxide dismutase (SOD); and levels of Bcl-2 and NF-κB protein in lung tissues. Lung carcinogenesis was induced by B[a]P (50mg/kg, intraperitoneally). Pre-treatment and post-treatment groups were treated with ESC (50mg/kg, per oral). Oxidative stress-induced by B[a]P was decreased by ESC. Anti-apoptotic protein Bcl-2 and pleotropic regulator NF-κB are found to possess oncogenic roles in B[a]P induced carcinogenesis. Western blot analysis study showed alleviated levels Bcl-2 and NF-κB in ESC pre-treated and post-treated groups in comparison to B[a]P treated group. These results suggest the anti-initiating and apoptosis inducing property of ESC on pre- and post-treatment in B[a]P induced lung carcinogenesis in Swiss albino mice.