Xiasangju (XSJ) granules, a kind of traditional Chinese prescription, is composed of three kinds of herbal medicines, including Prunella vulgaris L., Morus alba L. and Chrysanthemum indicum L. Flavonoids and phenolic acids are active components of the three herbal medicines in XSJ granules. In this study, HPTLC by one development system was firstly developed for simultaneous detection of the three herbal medicines and 14 phenolic components. Rosmarinic acid, scopolin and linarin could be considered as the specific markers for the identification of Prunella vulgaris L., Morus alba L. and Chrysanthemum indicum L., respectively. Then UHPLC combined with quantitative analysis of multiple components by two internal reference standards (QAM-TIRS) method was developed for the simultaneous determination of 9 components using chlorogenic acid and rosmarinic acid as the internal reference standards, and the accuracy and feasibility of the QAM-TIRS method was evaluated. The developed HPTLC and UHPLC-QAM-TIRS methods were used to evaluate the quality of 16 batches of XSJ granules collected from different pharmacies, and it was found that there were significant differences on the content of active components of these samples. In conclusion, a comprehensive, convenient and reliable quality evaluation system was established to perfect the quality standards of XSJ granules, so as to promote the development of quality control of Chinese medicine prescriptions. This study was supported by the National Natural Science Foundation of China (82104354), Guangdong Basic and Applied Basic Research Foundation (2022A1515012154), the funding grant from University of Macau (MYRG2022-00198-ICMS), the Science and Technology Development Fund, Macau SAR (0070/2021/AGJ), and the funding grant from Guangzhou Baiyunshan Xingqun (Pharmaceutical) Co., Ltd. (CP-028-2021).