The present study was aimed to examine the influence of lycopene from tomatoes (LycT) on apoptosis in N-nitrosodiethylamine (NDEA) induced hepatocarcinogenesis. Female Balb/c mice were randomly divided into four groups i.e. Control, NDEA, LycT and LycT + NDEA. Hepatic tissue from NDEA treated mice exhibited enhanced expression of anti-apoptotic gene bcl-2 and decreased expression of pro-apoptotic genes caspase 3, 9 and p53 when compared to control group. LycT intervention to NDEA challenged mice exhibited enhanced expression of caspase 3,9 and p53 and decreased expression of bcl-2 when compared with NDEA treated animals. Enhanced DNA damage was revealed in NDEA and LycT + NDEA groups as revealed by comet assay. However, TUNEL assay indicated enhanced apoptosis in LycT + NDEA group when compared to NDEA group. Hepatic tissue of NDEA treated mice showed persistently high lipid peroxidation levels and glutathione redox ratio during the process of hepatocarcinogenesis. The observed enhanced apoptosis in LycT + NDEA group may be attributed to its differential effects on apoptosis associated genes and its ability to act as a pro-oxidant. These findings provide a rational mechanistic insight into the growth-inhibitory effects of lycopene against hepatic cancer. (C) 2013 Elsevier Inc. All rights reserved.