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BACKGROUND: Although growing body of evidences have identified a critical role for Receptor-interacting protein kinase 1 (RIP1) in mediating cell death signaling,its possible contribution to HCC progression remains unclear.MATERIAL AND METHODS: RIP-1 expression was detected on tumor and adjacent liver tissues from 210 HCC patients by immunohistochemistry assay.The follow-up information was analyzed to figure out the role of RIP-1 on HCC prognosis.The in vitro experiments were carried out to identify the underlying mechanism.RESULTS: It was found that expression of RIP1 was significantly up-regulated in HCC tissues than adjacent liver tissues from 81.9% HCC patients (P < 0.001) by IHC staining.Over-expression of RIP1 was found positively associated with HBV infection,advanced TNM staging,portal vein invasion and intra-hepatic metastases.Kaplan-Meier curves analysis indicated that patients with higher RIP1 expression in HCC tissues suffered from unfavorable postsurgical survival.Higher RIP1 expression in HCC tissues was also confirmed to be a independent poor prognostic predictor.Knockdown of RIP1 resulted in suppression of cell viability and proliferation and induced cell apoptosis in MHCC97h cells.Nevertheless,enforced expression of RIP1 promoted cell viability and proliferation of Huh7 cells and inhibited cell apoptosis.Mechanistic studies revealed that RIP1 exerted its function on HCC progression via activating AKT/Bcl-2/BAX signaling.CONCLUSION: Our results provided the evidence of RIP1 over-expression in HCC,and RIP1 could be a novel predictive factor of unfavorable prognosis in HCC patients.Activation of AKT/Bcl-2/BAX signaling contributed to RIP1 promoting HCC progression.