Flesh browning (FB) is a common physiological disease of apple fruit during cold storage, which physiological mechanism was revealed in the present study through analyzing physical, transcriptomic, and targeted metab-olomic parameters. A total of 8559 differentially expressed genes were identified between FB and normal flesh. In FB, the glycolysis/gluconeogenesis pathway was down-regulated; starch and sucrose metabolism, phenyl-propane biosynthesis, plant hormone signal transduction, mitogen-activated protein kinase signaling pathway, and plant-pathogen interaction were all up-regulated. In addition, FB was also associated with the expression level of genes related to defense, cold stress, and reactive oxygen species (ROS) scavenging, and various tran-scription factor families. Characteristics of FB tissue included lower contents of flavonoids and sugars, higher contents of jasmonic acid and ROS, lower organic acids contents and higher proportion of lactic acid/malic acid level. In conclusion, FB is a complex metabolic process, which involves the changes in the metabolites, genes expression, and transcriptional regulations in the primary metabolism, secondary metabolism, signal trans-duction and other pathways of apple fruit during cold storage.