In summary, our study provides new insights into the biological function of OTUB1 and NDUFS2, indicating that targeted therapy against OTUB1 and/ or NDUFS2 could hold the premise to provide a new therapeutic method for the treatment of pancreatic cancer, but the specific mechanism by which the OTUB1/NDUFS2 axis regulates the mitochondrial death of pancreatic cancer cells needs to be further experimentally investigated and consolidated. Here, OTUB1 is linked to pancreatic neoplasm.