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Siji-kangbingdu mixture is an anti-inflammatory, anti-bacterial, and anti-viral herbal mixture which is frequently used by doctors to treat upper respiratory infections. It’s important to establish an efficient and economical quality-control method to ensure the quality consistency and efficacy stability of Siji-kangbingdu mixture. In this study, an integrated multi-evaluation method was established, sequentially involving UPLC-TripleTOF-MS analysis, UPLC fingerprint analysis, and the quantitative analysis of multi-components using the single-marker (QAMS) method. With one chromatographic condition, a total of 71 compounds were identified by MS and MS/MS information, with a mass error of less than 5 ppm; 49 peaks detected in 254 nm were selected to establish the fingerprint similarity model, and 7 chemical compounds were simultaneously determined, namely, chlorogenic acid, liquiritin, rutin, isochlorogenic acid A, forsythin, forsythoside A, and glycyrrhizic acid, with forsythoside A as the reference standard. There was no significant difference in the content of the seven compounds between the QAMS method and the external standard method (ESM). The established multi-evaluation method will largely promote the quality control and standardization process of Siji-kangbingdu mixture. It also provides a reference workflow for the overall evaluation of TCM patent medicines, from chemical profiling to fingerprint and quantitative analysis.