Lipid peroxidation is highly associated with chronic degenerative diseases such as cancer. 4-hydroxy-2-nonenal is one of the major products of lipid peroxidation. 4-hydroxy-2-nonenal can interact with biomolecules, changing their conformation and activity. This study presents 4-hydroxy-2-nonenal-protein adducts formation in the first stages of Long-Evans Cinnamon rat hepatitis, a well recognized model for oxidative stress-associated hepatocarcinogenesis. 4-hydroxy-2-nonenal-protein adducts appeared in hepatocyte cytoplasm before the beginning of hepatitis and their presence was very strong during hepatitis, while a transient perinuclear expression of 4-hydroxy-2-nonenal-protein adducts was shown mainly at early hepatitis stages. 4-hydroxy-2-nonenal-protein adducts formation correlated to the expression of the tumour marker glutathione S-transferase P-form. These results show that lipid peroxidation modification of proteins might be implicated in the first stages of hepatocyte cancer initiation in Long-Evans Cinnamon rats.