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• DEHP presented low acute toxicity to adult zebrafish (Danio rerio) • DEHP induced oxidative stress, lipid peroxidation and DNA damage in zebrafish hepatic tissue. • Acetylcholinesterase (AChE) activity of zebrafish liver was significantly inhibited after DEHP exposure. • The ecotoxicological risk of adult zebrafish increased with increasing DEHP concentrations. Di-(2-ethylhexyl) phthalate (DEHP) has become a ubiquitous contaminant in aquatic environments due to its increasing utilization in recent years. Although its environmental risks to aquatic organisms have attracted widespread attention, the ecotoxicological effects and toxic mechanism of DEHP on zebrafish (Danio rerio) liver remain poorly understood. Herein, this study investigated the acute toxicity, oxidative damage, neurotoxicity, and DNA damage of DEHP on zebrafish at the individual, tissue, physiological and biochemical levels. Results showed that no evident lethal effects of DEHP on zebrafish were observed in all testing concentrations. But in the chronic toxicity test (28 days), superoxide dismutase (SOD) and catalase (CAT) activities in zebrafish liver mainly increased during the pre-and mid-exposure experiment and subsequently decreased after 28 days exposure, whereas the acetylcholinesterase (AChE) activities were always inhibited. By comparison, reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione S-transferase (GST) levels generally increased throughout the experiment, indicating that DEHP enhanced oxidative stress lipid peroxidation, and cytotoxicity of zebrafish liver. DEHP induced DNA damage in hepatocyte, which was positively correlated with changes in ROS levels (0.9874 ≥ R2 ≥ 0.7374). Based on the risk assessment results, the integrated biomarker response (IBR) values were positively correlated with the DHEP concentrations, suggesting that higher DHEP concentrations may cause much more serious detrimental effects to zebrafish liver. Overall, this study is of great significance for understanding the ecotoxicity and mechanism of DEHP on zebrafish. [ABSTRACT FROM AUTHOR]