This dataset supports a study investigating the proteomic consequences of pharmacological ULK1 modulation in triple-negative breast cancer. MDA-MB-231 cells were treated with the ULK1 activator LYN-1604 or the ULK1 inhibitor MRT68921 at EC50 concentrations (29.8 µM and 2.6 nM, respectively) for 24 h. Autophagic activity was evaluated by LC3 immunoblotting and fluorescence microscopy, and quantitative label-free LC–MS/MS was used to characterize global protein abundance changes following ULK1 activation versus inhibition. Differentially regulated proteins were further interpreted using interaction network analysis and pathway enrichment approaches to identify convergent tumor-related and immune-associated signatures linked to ULK1 perturbation.