It is widely accepted that in chemical carcinogenesis different modes-of-action exist, e.g. genotoxic (GTX) versus non-genotoxic (NGTX) carcinogenesis. In this context, it has been suggested that oxidative stress response pathways are typical for NGTX carcinogenesis. To evaluate this, we examined oxidative stress-related changes in gene expression, cell cycle distribution and (oxidative-) DNA damage in human hepatoma cells (HepG2) exposed to GTX-, NGTX- and non-carcinogens, at multiple time points (4-8-24-48-72h). Two GTX (Azathriopine, AZA/Furan), two NGTX (Tetradecanoyl-phorbol-acetate, TPA/Tetrachloroethylene, TCE) carcinogens as well as two non-carcinogens (Diazinon, DZN/D-mannitol, Dman) were selected, while per class one compound was deemed to induce oxidative stress and the other not. Oxidative stressors AZA, TPA and DZN induced a 10-fold higher number of gene expression changes over time compared to Furan, TCE or Dman treatment. Genes commonly expressed between AZA, TPA and DZN, were specifically involved in oxidative stress, DNA damage and immune responses. However, differences in gene expression between GTX and NGTX carcinogens did not correlate to oxidative stress or DNA damage, but could instead be assigned to compound-specific characteristics. This conclusion was underlined by results from functional readouts on ROS formation and (oxidative) DNA damage. Therefore, oxidative stress may represent the underlying cause for increased risk of liver toxicity and even carcinogenesis: however, it does not discriminate between GTX and NGTX carcinogens.