T0001 is a recombinant human TNFR-Fc fusion protein mutant; it exhibits higher affinity to TNFα than etanercept and is now being tested in a Phase 1 study in China (ClinicalTrials.gov Identifier: NCT02481180). T0001 can inhibit the binding of soluble TNFα (sTNFα) or membrane-bound TNFα (mTNFα) to TNF receptors. When bound to mTNFα, the Fc-bearing TNFα antagonists have the potential to induce Fc-mediated effects, such as antibody-dependent cellular cytotoxicity (ADCC) and complement-mediated cytotoxicity (CDC) as well as outside-to-inside signals (apoptosis mainly). Recent studies have shown that ADCC may also play an important role in Crohn's disease (CD) and ulcerative colitis (UC). In this study, T0001 presented a higher binding activity on mTNFα than etanercept and similar binding activity with adalimumab and infliximab. Upon the addition of sTNFα, adalimumab and infliximab showed significantly increased binding to FcγRIIIa and C1q than T0001 and etanercept. T0001 exhibited significantly higher ADCC and CDC activity than etanercept, and the potency and the reporter response of T0001 were very close to adalimumab and infliximab in ADCC reporter gene assays. And the similar potency of T0001 was also corroborated by PMBC-based ADCC assay. T0001, but not etanercept could induce apoptosis, while adalimumab and infliximab were more effective. These results suggest that T0001 may not only exert improved efficacy in treating rheumatoid arthritis (RA) because of its high affinity to sTNFα but also has a therapeutic potential in CD and UC due to its increased binding to mTNFα with resultant Fc-associated functions (ADCC, in particular) and improved apoptosis.