In summary, we have, for the first time, performed quantitative phosphoproteomics to study the effects of bortezomib on MM cells. The current results expand the list of bortezomib-targeted phosphoproteins and their phosphorylation sites. Especially, our functional studies indicated that bortezomib-induced phosphorylation of stathmin promotes cell death and that the bortezomibinduced changes in the MT stabilization can be attributed to the bortezomib-induced phosphorylation of stathmin. Our comprehensive study of phosphorylation regulation in proteasome inhibition in MM cells may serve as a valuable resource for future research in the field and thus advance the general mechanistic understanding of bortezomib in MM.