Xianling Gubao is a common and effective medicine in the treatment of orthopedic diseases. In recent years, it has been reported to be associated with liverinjury. However, through the analysis of the adverse drug reactionreports and key hospital cases, we found that there is considerable incomplete information in the reports of Xianling Gubao-related liverinjury cases retrieved from the literature. Thus, it is difficult to accurately judge causality between the drug and liverinjury. Six cases of liverinjury related to Xianling Gubao were identified in key hospitals, two of which achieved the clinical diagnosis according to the assessment of the integrated evidence chain method. We further analyzed the public health data of all residents in Yinzhou. The gross incidence rate of Xianling Gubao-related liverinjury was 0.034%, which corresponds to a level of rare incidence. This revealed that Xianling Gubao-related liverinjury has significant divergence in individuals and an idiosyncratic nature. The gross incidence of liverinjury related to Xianling Gubao was lower than that of other medicines for the treatment of orthopedic diseases. Based on the idiosyncratic drug-induced liver injury model mediated by immune stress, it was found that Epimedii Folium and Psoraleae Fructus were the major components that lead to liverinjury, and the liverinjury caused by a full prescription was less serious than that encountered with only Epimedii Folium and Psoraleae Fructus. This suggests that the other 4 herbs (Dipsaci Radix, Anemarrhenae Rhizoma, Rehmanniae Radix,Salviae Miltiorrhizae Radix et Rhizoma) can prevent/alleviate the liverinjury. Through disassembled prescriptionanalysis, we found that the attenuation efficacy of Salviae Miltiorrhizae Radix et Rhizoma was the most significant. In conclusion, Xianling Gubao may cause idiosyncratic liverinjury in a tiny minority of susceptible individuals, but the incidencerisk is lower than that of other commonly used drugs for orthopedic disease. Xianling Gubao should be discreetly applied to patients with immune stress. The major components that induced liverinjury in Xianling Gubao were Epimedii Folium and Psoraleae Fructus, and Salviae Miltiorrhizae Radix et Rhizoma appears to attenuate this toxicity. This study provides a reference for the rational clinical medication with Xianling Gubao.