Tumour necrosis factor (TNF)-alpha-induced protein 8-like 2 (TIPE2 or TNFAIP8L2) is a novel identified negative regulator of both innate and adaptive immunity, which participates in immune homeostasis. TIPE2 is expressed in both immune tissues and non-immune tissues. It is significantly down-regulated in patients with infectious and autoimmune diseases, and the depletion of TIPE2 causes severe inflammatory disease. In recent years, accumulating evidence has shown that TIPE2 serves as an ideal biomarker and as a tumour suppressor in several tumour types. In this review, we summarized the roles and corresponding mechanisms of TIPE2 in immune regulation and different diseases, especially in tumourigenesis.