Abstract: 【Objective】 This study compared the composition and content differences of polyphenols in Lycium barbarum from different origins, cultivars and interannual periods, with the aim of providing a new guarantee for the in-depth study of food bioactivities of dual-purpose medicine and food, as well as the development of new products. 【Methods】 90 Lycium barbarum samples were collected from three provinces of Xinjiang, Ningxia and Gansu, and the contents of 20 polyphenolic compounds were simultaneously determined by liquid chromatography-mass spectrometry (LC-MS), and the differences between different origins, varieties and interannual periods were analysed using analysis of variance (ANOVA) and LSD multiple comparison method, and combined principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) for analysis. 【Results】 The results showed that there were significant differences in the content and composition of polyphenolic compounds in Lycium barbarum from different production origins, varieties and interannual periods (P<0.05).The top three polyphenolic compounds in Lycium barbarum samples from provinces and origins were p-coumaric acid (4.06±1.99) mg/kg, quinic acid (3.77±1.31) mg/kg and ferulic acid (1.32±0.83) mg/kg. The contents of 20 polyphenols in Xinjiang and Ningxia Lycium barbarum were significantly higher than those in Gansu (P<0.05); the total contents of 20 polyphenol compounds in Ningqi 7# and Ningqi 9# samples were significantly higher than those in Ningqi 5# (P<0.05); the contents of flavonoids in 2022 Lycium barbarum samples were significantly higher than those in 2021 (P<0.05). A significant positive correlation between the content of quercitrin, quercetin, cryptochlorogenic acid, caffeic acid and p-coumaric acid and the total polyphenol content. The principal component analysis shows that the cumulative contribution rate of PC₁ and PC₂ from different origins, different varieties and different years is 72.54%, 75.87% and 80.4%, respectively, which can better reflect the comprehensive information of Lycium barbarum polyphenols and effectively discriminate Lycium barbarum from different origins. 【Conclusion】 The content of monomeric polyphenolic compounds in Lycium barbarum is strongly influenced by origin and inter-years, but less influenced by cultivar factors. The content of coumaric acid in Lycium barbarum is high, while the phenolic composition and relatively high.