Phytochromobilin (PΦB) participates in the regulation of plant growth and development as an important synthetase of photoreceptor phytochromes (phy). And Arabidopsis Long Hy-pocotyl 2 (HY2) appropriately works as a key PΦB synthetase. However, whether HY2 takes part in plant stress response signal network remains unknown. Here, we described the func-tion of the HY2 in NaCl signaling. The hy2 mutant was NaCl-insensitive, whereas HY2-overexpressing lines showed NaCl-hypersensitive phenotypes during seed germination. The exogenous NaCl induced the transcription and the protein level of HY2 which positively mediated the expression of downstream stress-related genes of RD29A, RD29B and DREB2A. Further quantitative proteomics showed the patterns of 7,391 proteins under salt stress. HY2 was then found to specifically regulate 215 differentially regulated proteins (DRPs) which, according to GO enrichment analysis, were mainly involved in ion homeostasis, flavonoid biosynthetic & metabolic, hormone response (SA, JA, ABA, ethylene), reactive oxygen spe-cies (ROS) metabolic, photosynthesis and detoxification pathway to respond to salt stress. More importantly, ANNAT1-ANNAT2-ANNAT3-ANNAT4 and GSTU19-GSTF10-RPL5A-RPL5B-AT2G32060, two protein interaction networks specifi-cally-regulated by HY2, jointly participated in the salt stress response. These results direct the pathway of HY2 participating in salt stress, and provide new insights for the plant to re-sist salt stress.