Nickel sulphate (NiSO4) is a common industrial substance employed in various applications such as electroplating, battery production, and metal coating. However, its continuous occupational and environmental exposure has elicited toxicological issues. This review is a critical assessment of the histopathological, biochemical and molecular alterations of the liver in mice exposed to nickel sulphate, correlating the findings from both animal and mechanistic tests. Studies evidently show that NiSO4 leads to dose-related liver cell damage, necrosis, steatosis, inflammatory infiltration, and degeneration in animals, closely linked to the increase of serum transaminases and oxidative-stress biomarkers. From a mechanistic perspective, nickel exposure affects redox homeostasis, mitochondrial integrity, and lipid metabolism leading to ferroptosis, apoptosis, and endoplasmic reticulum stress signalling. Additionally, comparative data analysis between hepatic injuries induced by soluble and particulate nickel salts shows that the former is more fatal, highlighting the relevance of compound bioavailability and exposure pathway. The hepatoprotective effects of antioxidants and flavonoid supplements (e.g. selenium, silymamarin, hesperidin, etc.) against hepatic injury are seen in preclinical models. Cross-species researchers also show that there are conserved oxidative and inflammatory systems of damage, suggesting it may be applicable in human risk assessment. According to the review, early biomarkers, multi-omics, and mechanistically directed interventions are needed to enhance toxicological assessment. Overall, long-term exposure to nickel sulphate is a realistic risk for hepatic damage; therefore, increased occupational preventive and mechanistic research should be used to improve preventive and therapeutic strategies.