The transcriptional factor SOX11 is a disease-defining antigen in mantle cell lymphoma (MCL) and absent in most non-malignant tissues. To explore the role of SOX11-related cell signaling, and potentially take benefit from these for targeted therapy, associated networks and proteins need to be defined. In this study, we used an inducible SOX11 knock-down system followed by gene expression analysis to identify co-regulated genes and associated signaling pathways. A limited number (n?=?27) of significantly co-regulated genes were identified, including SETMAR, HIG-2, and CD24. Further analysis confirmed co-regulation of SOX11 with HIG-2 and CD24 at the protein level. Of major interest, knock-down of HIG-2 reduced SOX11 levels and increased proliferation, the proteins are thus cross-regulated. HIG-2 was localized at the plasma cell membrane in both cell lines and primary MCL cells, and could potentially be of interest for targeted therapy.