Metastasis is the most challenging issue for gastric cancer, and identification of the molecular mechanism and suitable targets for treatment is the major purpose of recent research. In this study, we found the long non-coding RNA ANRIL was critical for the progression of gastric cancer. Knockdown of ANRIL (also known as CDKN2B-AS) with shRNA increased apoptosis, inhibited tumor growth, and suppressed migration of cancer cells. TET2 (Tet Methylcytosine Dioxygenase 2), a methylcytosine dioxygenase suppressed ANRIL function and prevented cancer progression. Patients with higher TET2 expression survived better, while with higher ANRIL survived worse. Furthermore, expressions of TET2 and ANRIL were negatively correlated in the patient samples. The mechanistic study suggested that ANRIL promoted tumor progression mainly by enhancing NF-kB signaling. Impact statement Gastric cancer is one of the leading causes of cancer-related death. The lack of curative therapeutic options ascribes to the complex genetic background and heterogeneity of gastric cancer. Understanding the molecular details of the disease and identifying the therapeutic targets would offer additional treatment options. Long non-coding RNA ANRIL was involved in the progression of many cancers, including gastric cancer, but the mechanism was unknown. The current study indicated that ANRIL supported tumor cell survival by inhibiting apoptosis and promoted metastasis by enhancing NF-kB signaling. NF-kB signaling was critical in tumor progression, and this study proved another long non-coding RNA that could regulate NF-kB signaling. ANRIL would be a potential biomarker and therapeutic target for gastric cancer prognosis and treatment.