Abstract: Objective: To find the material basis of antioxidant activity of Sedum aizoon L. based on the study of spectrum-effect relationship, which provided a certain reference for its quality control. Method: The fringerprint of Sedum aizoon L. from different areas were established by high performance liquid chromatography-electrochemical detection (HPLC-ECD) and the similarity of the samples were evaluated. At the same time, the spectrum-effect relationship between HPLC-ECD fingerprint of Sedum aizoon L. and antioxidant activity was studied by partial least squares regression analysis and grey correlation analysis. Results: The HPLC-ECD fingerprint of Sedum aizoon L was established. The similarity of the samples was high and 17 common peaks were obtained. Among them, the 12 components were identified with the standard solution, including gallic acid, protocatechuic acid, tryptophan, methyl gallate, epigallocatechin, caffeic acid, epigallocatechin gallate, iriflophene, myricitrin, isoquercitrin, rosmarinic acid and quercitrin. The spectrum relationship showed that the variables important in projection (VIP) scores of gallic acid, protocatechuic acid, epigallocatechin, epigallocatechin gallate, rosmarinic acid and quercitrin were greater than 1. Among them, the grey correlation degree of gallic acid, rosmarinic acid and quercitrin was nearly 0.8. Furthermore, epigallocatechin gallate, myricitrin, isoquercitrin, rosmarinic acid and quercitrin had higher libdock score in molecular docking. Therefore, epigallocatechin gallate, myricitrin, isoquercitrin, rosmarinic acid and quercitrin were the primary components contributing to the antioxidant activity of Sedum aizoon L.. Conclusion: The basis of antioxidant activity of Sedum aizoon L. was determined by the study of spectrum effect relationship with chemometrics, which provides a certain scientific basis for the quality evaluation of Sedum aizoon L..