Kinase dysregulation is greatly associated with cell growth, proliferation, differentiation and apoptosis, which indicates their great potential as therapeutic targets for treatment of numerous progressive disorders, including inflammatory, metabolic and autoimmune disorders, organ fibrosis and cancer. The c‑Jun N‑Terminal Kinase (JNK), as a member of MAPK family, is proved to be a potential target for the treatment of pulmonary fibrosis, which is the most common progressive and fatal fibrotic lung disease. As a new strategy, small-molecule-mediated targeted protein degradation pathway has the advantages of catalytic properties, overcoming drug resistance and expanding target space, which can circumvent the limitations associated with kinase inhibitors. Proteolysis targeting chimeras (PROTAC) contains a linker to concatenate a ligand of E3 ubiquitin ligase and a ligand for a protein of interest (POI). We developed a total of 20 JNK1-targeted PROTACs that induce proteasomal degradation of JNK1 components. The most active PROTAC molecule PA2 was then investigated by JNK1 enzyme assay and protein degradation assay, which suggested that PA2 had an anti-JNK1 ability and provided insights for the future use of JNK1-targeted PROTAC as treatment drugs for pulmonary fibrosis.