ETHNOPHARMACOLOGICAL RELEVANCE: Quality control is a powerful method for ensuring the effectiveness and safety of herbal medicines. Phyllanthus emblica L. fruit (PE) has been extensively used in both Ayurvedic and traditional Chinese medicine. However, the current Indian and Chinese pharmacopeias set a minimum concentration threshold of gallic acid to identify qualified PE samples, without providing a clear framework to distinguish superior-quality PE samples. AIM OF THE STUDY: To establish an efficacy-oriented quality grading framework for herbal medicines, using PE, a medicinal plant known for its hepatoprotective activity, as an example. METHODS: First, a mouse model of alcohol-induced liver injury was developed to evaluate the hepatoprotective effects of PE. Second, a combined strategy of serum pharmacochemistry, network pharmacology, metabolomics and experimental validation was employed to identify key quality markers (Q-markers) linked to the hepatoprotective effects of PE. Finally, PE samples from different sources were collected to assess their hepatoprotective activities and Q-marker concentrations. A discriminant analysis model was then developed to classify PE samples into different quality grades by using Q-marker concentration as the predictive factor and hepatoprotective activity as the evaluation criterion. RESULTS: PE significantly alleviated liver damage, as evidenced by a reduction in pathological abnormalities and serum aminotransferase levels. Six hepatoprotective Q-markers in PE were identified and verified, including gallic acid, methyl gallate, corilagin, chebulagic acid, ellagic acid and quercitrin. Significant variability in Q-marker concentrations and hepatoprotective effects was observed among different sources of PF samples, and a discriminant analysis model accurately classified PE samples into distinct quality grades. CONCLUSIONS: This study successfully established an efficacy-oriented quality grading framework for PE, providing a methodological approach for the quality classification of herbal medicines.