As a multi-base source traditional Chinese medicine, the hepatotoxicity of Uncariae Ramulus Cum Uncis (URCU) has been reported repeatedly in recent years. The lack of clarity of toxic components and toxicity mechanisms is a key issue that needs to be addressed. In this article, a "component-target-pathway" network strategy was established to firstly predicting the hepatotoxic components and the toxicity mechanism of URCU. Ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) and data post-processing technology were used to classify and identify the main components in Uncaria rhynchophylla (Miq.) Miq. ex Havil. (UR) and Uncaria sinensis (Oliv.) Havil. (US). Then, the potential hepatotoxic components were screened by network pharmacology and molecular docking. As a result, 40 components and 39 ingredients were identified in UR and US, respectively. Cadambine, rhynchophylline, corynoxeine, isocorynoxeine, strictosamide and mitraphylline were screened as the potential hepatotoxic ingredients contained both in UR and US. The network pharmacology showed that the potential hepatotoxic components could affect the IL-17 signaling pathway by regulating related targets such as MAPK1 and MAPK14, which might lead to the occurrence of liver injury. This study not only provided a reasonable strategy for the rapid screening of hepatotoxic components in URCU, but also supplied reference and guidance for the rational clinical application and scientific supervision of URCU.