Trypsin has a new activity of scavenging superoxide anion and generating hydrogen peroxide. Trypsin can significantly improve the storage quality of C. sativus. To illustrate the mechanism of trypsin-induced resistance in fruits and vegetables, an integrated analysis of widely targeted metabolomics and transcriptomics was carried out. Transcriptomic results showed that 1068 genes highly related to phenylpropanoid biosynthesis gathered in the brown module were obtained by WGCNA. In KEGG analysis, differentially expressed genes (DEGs) were also highly enriched in EIP (Environmental Information Processing) pathways “Plant hormone signal transduction (map04075)” and “MAPK signaling pathway-plant (map04016)”. Next, 87 genes were identified as the leading edge by GSEA analysis. So far, CsMYC2 was highlighted as a key transcription factor that regulates phenylpropanoid biosynthesis identified by GSEA and WGCNA. Furthermore, the major route of biosynthesis of phenylpropanoid compounds including coumarins, lignins, chlorogenic acid, flavonoids, and derivatives regulated by trypsin was also illustrated by both transcriptomic and metabolomic data. Results of O2PLS showed that CsMYC2 was positively correlated with Rosmarinic acid-3-O-glucoside, Epigallocatechin, Quercetin-3-O-sophoroside (Baimaside), and so on. Correlation between CsMYC2, phenylpropanoid related genes, and metabolites in C. sativus was illustrated by co-expression networks. Roles of CsMYC2 were further checked in C. sativus by VIGS. The results of this study might give new insight into the exploration of the postharvest resistance mechanism of C. sativus induced by trypsin and provide useful information for the subsequent mining of resistance genes in C. sativus. Display omitted •CsMYC2 identified as a hub transcription factor responses to trypsin in C. sativus.•Route of phenylpropanoid biosynthesis regulated by CsMYC2 was rewired in C. sativus.•Trypsin induced C. sativus resistance through JA rather than ABA or other hormones.