Abstract: Objective : To investigate the effect of the Osteopontin (OPN) and Nuclear factor-κB p65 (NF-κB p65)on the invasion and metastasis of gastric cancer. Methods : The expression of OPN and NF-κB p65 were detected in 12 cases of non-cancerous gastric tissue and 72 cases of gastric cancer tissue by using immunohisto-chemistry. Results : 1) The postive rates of OPN and NF-κB p65 expression were 0 in all the 12 cases of non-cancerous gastric tissue, 43.30% and 40.00% respectively in 30 case gastric cancer without lymph nodes metastasis, 76.92% and 73.07% respectively in 26 case gastric cancer with lymph nodes metastasis, and 87.50% and 81.25% respectively in 16 cases of gastric cancer with metastasis of the lymph nodes and the other organs. 2) The positive rates of OPN and NF-κB p65 expression have distinct difference in the gastric cancer with metastasis of lymph nodes and other organs or without lymph node metastasis (P_a =0.004,P_c=0.007), and also have distinct difference in gastric cancer with lymph nodes metastasis and without lymph node metastasis (P_b=0.011, P_d=0-013). 3)The positive expressions of OPN and NF-κB p65 have distinct differences and are related respectively.(P₁=0.042, r₁=0.670). conclusions : Over-expressions of OPN and N F-κB in the invasion and metastasis of gastric cancer are closely related to the invasion and metastasis of the gastric cancer.