It has been revealed by us that superoxide scavenging is a new activity of trypsin. In this study, the synergistic mechanisms of trypsin and superoxide dismutases (SODs) were evaluated in Hylocereus undatus (pitaya). Trypsin significantly improved the storage quality of H. undatus, including weight loss impediment and decrease of cellular injury. The regulatory mechanisms of 16 SOD genes by trypsin were revealed using transcriptomic analysis on H. undatus. Results revealed that important physiological metabolisms, such as antioxidant activities or metal ion transport were induced, and defense responses were inhibited by trypsin. Furthermore, the results of protein-protein interaction (PPI) networks showed that besides the entire ROS network, the tiny SODs sub-network was also a scale-free network. Cu/Zn SODs acted as the hub that SODs synergized with trypsin during the storage of H. undatus.Trypsin is a widely used protease. It has been confirmed that trypsin significantly impacts on the free radical scavenging activities of flavonoids [8]. Our previous results also showed that trypsin scavenges superoxide anions (O 2 • − ) and protects cells [9].In the area of phytopathology, transcriptomic analysis has been successful used on lots of plants [10][11][12][13]. However, few of transcriptomic works have been focused on the preservation of fruits. The mechanisms of betalain biosynthesis have been investigated in H. undatus [2], and the concision analysis of antioxidant system induced by trypsin has also been investigated in our previous paper [14]. Considering the superoxide scavenging activity of trypsin, the function and synergistic mechanisms of trypsin with SODs impact on the quality of H. undatus during storage is an interesting work. The mechanisms of postharvest quality of fruits still need more works.Protein-protein interaction (PPI) networks analyses help us to figure out the regulatory mechanisms of proteins [15]. Plugins of Cytoscape, including NetworkAnalyzer, Molecular Complex Detection (MCODE), and cytoHubba, could score and rank the nodes or obtain clusters in the PPI network [16].In the current work, the regulatory mechanisms of trypsin on the H. undatus by cooperating with SODs were investigated. The changes in expression of SODs of H. undatus peels were analyzed. Analyses of gene ontology (GO) and KEGG enrichment of ROS or SOD related genes were performed, and the PPI network of ROS related genes and sub-network of SODs and their first neighbors were constructed. The hub genes of SODs regulated by trypsin during storage were further screened by cytoHubba and MCODE of cytoscape.