Background: Annona cherimola Mill. (A. cherimola) is mainly characterized by its antioxidant and cytoprotective properties due to their content of phenolic compounds. Objective: To evaluate antioxidant and hepatoprotective activity of ethanol extract of leaves from A. cherimola against induced toxicity by paracetamol in rats. Methods: Amount of total phenolics compounds of ethanol extract of A. cherimola Mill. was determined by the Folin-Ciocalteu method and antioxidant activity was evaluated by DPPH method. Three doses of the ethanol extract of leaves of A. cherimola (250, 500 and 750 mg/Kg/day) were administered to rats and it was evaluated biochemical blood parameters: aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were measured, liver tissue was removed for histopathological analysis. Results: Ethanol extract of leaves from A. cherimola had 41.26 mg GAE/g extract and antioxidant DPPH Scavenging Activity had 85.51%. A. cherimola reduced blood levels of ALT, AST and ALP, compared to control group Paracetamol, ethanol extract, being more effective at doses of 750 mg/Kg/day. Histopathological evaluation suggested that A. cherimola decreased hepatic necrosis and degenerative process induced by paracetamol. Conclusions: Hepatoprotective activity of ethanol extract of leaves of A. cherimola was demonstrated, being hepatoprotective activity dose dependent and the mechanism may involve antioxidant activity and total polyphenols found in extract of this plant.