This study investigated the effects of mercury chloride (HgCl2 ) on the deposition of mercury (Hg), histopathology and oxidative stress in liver and kidney of laying hens. The gene expressions of antioxidant enzymes and nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) were further studied to uncover the molecular mechanism. A total of 960 40-week-old Hyline brown laying hens were randomly allocated to five treatments with eight pens per treatment and 24hens per pen. The hens were fed with five experimental diets containing graded levels of Hg at 0.270, 1.250, 3.315, 9.405 and 27.230mg/kg respectively. Results revealed that both deposition of Hg and score of injury in liver and kidney were significantly increased as dietary Hg dosage up to 27.230mg/kg diet. Deposition of Hg was positively related to score of injury in liver and kidney of laying hens. Besides, the activities of superoxidative dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GSH-Px), and glutathione (GSH) content all significantly decreased (p<0.05), while malondialdehyde (MDA) content significantly increased (p<0.05) after Hg exposure in liver and kidney of laying hens. In addition, positive relationships occurred between antioxidant enzyme activities and antioxidant enzyme gene expressions except between SOD activity and manganese superoxide dismutase (MnSOD) gene expression in liver. Meanwhile, Nrf2 gene expression was positively related to antioxidant gene expressions and negatively connected with Keap1 gene expression. Negative relationships occurred between Nrf2 and Keap1 protein levels in liver and kidney. In conclusion, Hg could dose-dependently damage liver and kidney and induced hepatic and renal oxidative stress by means of suppressing Nrf2-Keap1 signalling molecule in laying hens.