IntroductionLiuweizhiji Gegen‐Sangshen (LGS) oral liquid is a Chinese patent medicine that is widely used for the prevention and treatment of alcoholic liver disease in clinical practice. However, the chemical complexity of LGS has not yet been investigated.ObjectiveThe aim of this study was to rapidly identify chemical constituents of LGS and establish a quality control method based on fingerprint and quantitative analysis.MethodologyA comprehensive strategy was used by combining qualitative analysis by ultra‐performance liquid chromatography tandem quadrupole time‐of‐flight mass spectrometry (UPLC‐Q‐TOF‐MS) and fingerprint analysis by high‐performance liquid chromatography with diode array detection (HPLC‐DAD).ResultsA total of 162 chemical components in LGS, including 91 flavonoids, 31 organic acids, and 20 phenolic compounds, were identified or preliminarily characterized in both positive and negative ion modes based on the UPLC‐Q‐TOF‐MS results. Of these, 37 were confirmed with the reference standards. In fingerprint analysis, 23 peaks were chosen as common peaks and used to evaluate the similarity of different batches of LGS. Subsequently, a rapid quantification method was optimized and validated for the simultaneous determination of multiple chemical markers in LGS. The validated quantitative method was successfully used to analyze different batches of LGS samples.ConclusionThe proposed comprehensive strategy combining HPLC‐DAD fingerprinting and multi‐component quantification demonstrated satisfactory results with high efficiency, accuracy, and reliability. This can be used as a reference for the overall quality consistency evaluation of Chinese patent medicines.