This study aims to establish a quantitative control method for multi-index components of Epilobium hirsutum, and to evaluate the quality of E. hirsutum from different producing areas by combining chemometrics, weighted technique for order preference by similarity to an ideal solution(TOPSIS) and grey relational analysis(GRA) fusion model. The COSMOSIL AR-Ⅱ C₁₈ was used, the mobile phase was acetonitrile-0.1% phosphoric acid aqueous solution. The detection wavelength were 280, 360, and 210 nm. The content of each component was calculated by quantitative analysis of multi-components by single marker(QAMS) method with protocatechuic acid, kaempferol and oleanolic acid as internal reference substances. The alcohol soluble extracts, total ash and acid-insoluble ash were detected according to the general principles of Chinese Pharmacopoeia (2020 Edition). The data were studied by chemometric analysis, and a weighted TOPSIS and GRA fusion model was established. The methodological verification met the requirements of Chinese Pharmacopoeia (2020 Edition). The relative correction factor has good durability, and the calculation results of QAMS method are close to those of external standard method. The results of chemometrics analysis showed that 16 batches of E. hirsutum were clustered into three categories, quercetin, crategolic acid, gallic acid, kaempferol, hyperoside and protocatechuic acid were the differential markers affecting the quality of E. hirsutum. The relative closeness of 16 batches of samples was between 0.3703 and 0.617 8. The established HPLC multi-index quantitative method is easy to operate and can be popularized, and the fusion model of Chemometrics combined with weighted TOPSIS and GRA can provide reference for evaluating the quality of E. hirsutum from different habitats.