Updated project metadata. Accurate analysis of tissue-specific secretory proteins in blood plasma can provide valuable information regarding therapeutic target development but current approaches are mostly limited to ex vivo proteomic analysis. Here, we developed an in situ secretory protein labeling technology using endoplasmic reticulum-anchored TurboID (iSLET) and validated its utility in vivo by the successful identification of liver-specific secretory proteins in mouse plasma. iSLET is a promising new strategy that will facilitate the discovery of tissue-specific secretory proteins mediating interorgan communication in normal physiology and disease.