Receptor-interacting protein kinase 3 (RIP3) is a member of the RIP Ser/Thr kinase family, plays an important role in regulating cell survival, cell apoptosis and cell necrosis. However, the role of RIP3 in the carcinogenesis of colorectal cancer is still poorly understood.We used quantitative PCR and Western blot analysis to examine RIP3 expression in primary colorectal cancer and paired normal colorectal mucosa. RIP3 clinicopathological significance was assessed by immunohistochemical staining in 112 cases of primary colorectal cancer paired with noncancerous tissues. The biological function of RIP3 overexpression was measured by CCK8 assay and plate colony formation assay. Dual staining with fluorescent Annexin V and propidium iodide (PI) was used to discriminate apoptotic or necrotic cell death.RIP3 expression was significantly lower in colorectal cancer and associated with T stage, M stage and AJCC stage. Cox proportional hazard models showed that RIP3 expression was an independent prognostic factor for overall survival and disease-free survival in patients with colorectal cancer. Overexpression of RIP3 significantly suppressed the proliferation of colorectal cancer cells in vitro.Our results suggest that RIP3 may function as a novel prognostic indicator after surgery and play a suppressive role in the colorectal carcinogenesis.