We found SENP1 was upregulated in MCL patient samples and cell lines; knockdown of SENP1 inhibited MCL cell proliferation and promoted cell apoptosis, and also inhibited MCL tumor growth in mice; mechanically, knockdown of SENP1 resulted in an increased expression of tumor suppressor cytokine signaling 2 (SOCS2) by inhibiting the JAK-STAT5 activity. Here, SOCS2 is linked to mantle cell lymphoma.