To determine the anti-tumor effects induced by interfering CXCR4 receptor oligomerization, we treated the cells with a small molecule and a nanobody in the Z-138 cell line (mantle cell lymphoma, MCL), separately. By using phospho-enrichment method, we identified 15,563 phosphopeptides and quantified more than 15,000 phosphosites. Deep phosphoproteome profiling enables us to characterize the phosphorylation changes upon the disruption of CXCR4 oligomerization on the cell surface. Followed pathway analysis shows that phosphorylation changes in apoptotic regulation were found upon the treatment of drugs. Hence, we speculated that inhibition of CXCR4 oligomerization may sensitive Z-138 cells to apoptosis in combination with another therapeutic trigger.