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The receptor-interacting protein-1 (RIP-1) is an important molecular in inflammation signaling pathways, but the role of RIP-1 in gastric cancer is largely unknown. In this study, we tested the expression of RIP-1 in gastric cancer samples and analyzed the effects of expression of RIP-1 on the prognosis in gastric cancer patients. We analyzed the role of the RIP-1 in gastric cancer cells and addressed the functional role of RIP-1 using a xenograft mouse model. A lentivirus-based effective RIP-1 siRNA vector was infected into HGC and AGS cells. The effect of RIP-1 siRNA on HGC and AGS cells were investigated by cell proliferation assay and invasion assay. Furthermore, we examined the role of RIP-1-siRNA on HGC cells in the mice with subcutaneous xenograft tumor, and preliminarily analyzed the underlying mechanisms. The results indicated that the expression of RIP-1 in the gastric cancer tissues was significantly higher than the expression in the normal gastric tissues. Additionally, RIP-1 immunoreactivity was positive at the site of invasion, but little or no immunoreactivity was detected at the gastric cancer parts of interstitial substance. Gastric cancer patients with high expression of RIP-1 had a poor survival rate. RIP-1 expression in the gastric cancer cell lines were general. HGC-R-1-RNAi-LV inhibited HGC and AGS cell proliferation and invasion ability in vitro. RIP-NF-κB/AP-1-VEGF-C signaling pathways have a crucial role in the regulate the biological functions of HGC cells. HGC-R-1-RNAi-LV suppressed tumor growth in the HGC cell subcutaneous xenograft model. In conclusion, our data indicate that RIP-1 promote the growth and invasion of gastric cancer in vitro and in vivo, additionally providing evidence that targeting RIP-1 may be useful in the treatment of gastric cancer.