To explore the processing mechanism of Aurantii Fructus decoction pieces used in Guangdong province and Hong Kong by analysing the chemical variation between raw and processed Aurantii Fructus with different methods based on UHPLC-Q-TOF-MS. The total ion chromatograms detected in positive and negative ion modes, and ion peak area ratio before and after processing were taken as variation indexes in the comparison. The results indicated that fermented Aurantii Fructus could produce three new ingredients, namely eriodictyol-7-glucoside, hesperetin-7-O-glucoside and 5-demethylnobiletin. At the same time, it could significantly increase the content of naringenin and hesperetin components, and could increase the content of such limonin derivatives as sudachinoid A, obacunoic acid and limoninand nomilinic acid. This suggests that the fermentation processing method of Aurantii Fructus decoction pieces used in Guangdong province and Hong Kong is of important significance for enhancing biological activity and bioavailability, and improving the clinical efficacy of Aurantii Fructus decoction pieces, and so is worth further protection and promotion.