In this study, we designed and synthesized a PROTAC named dEALK1 to degrade EML4-ALK protein, and also dEALK1Me that cannot exert degradation function served as a negative control. Mass spectrometry-based tandem mass tag-labeled quantitative proteomics was performed to evaluate the potential off-target effect of dEALK1 in H3122 cells treated with dEALK1 or dEALK1Me for six hours. The results showed that significant depletion of EML4-ALK proteins was only identified in cells treated with dEALK1, but not dEALK1Me, indicating that dEALK1 exerts a highly selective effect on stability of EML4-ALK protein.