Abstract: In recent years, the report of adverse reactions of traditional Chinese medicines (TCMs), especially the traditional non-toxic TCM-induced liver injuries have been arising, causing serious concerns about the safety of TCM from the public with heated controversy. Previous studies have focused on the direct toxic components of TCM, with little attention and research on idiosyncratic drug-induced liver injury (IDILI). Our team has established the new field of research on the TCM-related IDILI, and confirmed the objectivity and immune-specific properties of liver injury caused by a series of traditional non-toxic TCMs such as Polygonum multiflorum using the integrated evidence chain-based identification strategy for IDILI. Especially, we presented a novel and clinic-associated safety assessment strategy, namely “disease-syndrome-based toxicology”, for TCMs, which can systematically access the susceptibility mechanism of IDILI casued by Polygonum multiflorum and Epimedium. On this basis, we first proposed and established a three-dimensional pharmacovigilance system of TCM based on the identification of susceptible population, quality control of susceptible substances and clinical precise drug use as a comprehensive prevention and control method, which could be applied for the TCM safety risk prevention and control countermeasures against a series of IDILI. The safety evaluation and control of TCM was transformed from simply “finding toxicity with medicine” to combining it with “avoiding toxicity for patients”, which could effectively guide clinical safe and rational use of drugs. This paper reviews the research progress of IDILI in recent years in order to provide guidance and support for clinical safe and rational use of drugs and follow-up research.