TRIM (tripartite motif) family proteins, comprising RING finger, B-box and coiled-coil domains, are involved in various cellular processes including tumour development and antiviral response. One of the family proteins, TRIM31, was originally identified as a gene induced by growth-suppressive retinoid. Our previous study showed that TRIM31 is up-regulated in stomach cancer and that TRIM31 protein possesses the common features of the TRIM protein family, for example, ubiquitin ligase activity and homo-oligomerization tendency. Interestingly, TRIM31 negatively regulates growth of certain cell types despite its overexpression in gastric cancer tissues. We herein demonstrated that upon exogenous expression in 293 cells, TRIM31 is polyubiquitylated, which promotes its degradation in the proteasome pathway. The proteasome-mediated degradation of endogenous TRIM31 was further confirmed in AsPC-1 pancreatic cancer cells. Thus, this posttranslational modification governs the intracellular abundance of TRIM31, which is also dependent on inducible transcription as well as alternative splicing. The complicated control of the intracellular TRIM31 protein level may relate to its seemingly contradictory behaviours in the cancer pathology or the urgent response to viral infection.