Abstract: The method of UPLC-Triple TOF MS/MS combined with multivariate statistical analysis was used to study the differences of chemical compositions in Xanthii Fructus before and after stir-frying. Through the analysis of the multistage tandem mass spectrometry, the characteristic peaks were extracted with mass spectrometry data peak matching, peak alignment, noise filtering. Principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) were used for data processing. The chemical compositions were identified and tentative presumed according to MS accurate mass and MS/MS spectrometry fragmentation information, combined with the software of database search and comparison with reference standards and literature. The results show that the chemical compositions in Xanthii Fructus before and after stir-frying are clearly distinguished. A total of 44 different chemical compositions are detected in Xanthii Fructus before and after stir-frying, and 41 chemical compositions of which are identified. Among of them, there are 10 kinds of common differential compositions, such as liquiritigenin 4′-O-apiosyl-O-glucoside, 3′,4′,5,7-tetramethoxyflavone, chlorogenic acid, deoxyadenosine, 4-dicaffeoylquinic acid, 1,3-dicaffeoylquinic acid, 3,4-dicaffeoylquinic acid, astragalin, 4′-desulphate-atractylosid and β -carotene, which present different change laws. In the 10 differential components, the contents of liquiritigenin 4′-O-apiosyl-O-glucoside, deoxyadenosine, 1,3-dicaffeoylquinic acid, 3,4-dicaffeoylquinic acid, astragalin, and β-carotene are much higher in Xanthii Fructus after stir-frying, while the contents of 3′,4′,5,7-tetramethoxyflavone, chlorogenic acid, 4-dicaffeoylquinic acid, and 4′-desulphate-atractylosid are lower. This study provides a basic information for revealing the change law of chemical compositions in Xanthii Fructus before and after stir-frying.