The safe use of orthodox drugs and natural product-derived healthy supplements is always a public concern. Comparing with the orthodox drugs, there are less awareness and investigation on the adverse effects/toxicity induced by natural products. Natural products consist of multiple ingredients acting on multiple targets, which makes the investigation of their adverse effects/toxicity much more difficult and challenging. Among drug-induced toxicities, drug-induced liver injury (DILI) is one of the leading causes of acute liver failure. Unlike well-recognized DILI caused by orthodox drugs, the hepatic impairments caused by natural products, including herbal remedies, often have less public awareness and are also lack of confirmative diagnosis in clinic, although herb-induced liver injury (HILI) has been reported as one of the major causes of DILI worldwide. The diagnosis of HILI is challenging due to the lack of characteristic clinical features and specific biomarkers for the diagnosis. This has subsequently hindered the development of specific and efficacious treatment. Among differential natural products caused HILI, pyrrolizidine alkaloids (PAs) are one of the most significant and responsible phytotoxins. To date, over 660 PAs have been identified in approximately 3% of flowering plants, and about half of PAs have been reported to be hepatotoxic. Yearly, numerous incidences of PA-induced liver injury (PA-ILI) associated with the intake of PA-producing herbal products and/or PA-contaminated foodstuffs have been reported worldwide. In this presentation, using PA-ILI as an example, our methodical translational study, from the identification of clinical problems, to the laboratory basic science for delineating toxic mechanism and developing the mechanism-based biomarker, and then the transformation of the biomarker to clinical diagnosis of PA-ILI will be illustrated. [The study was supported by GRF Grants (Ref No.: 14110714, 14111816 and 14160817), and CUHK Direct Grant (Ref No.: 4054376)]