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The interaction of PD-1/PD-L1 allows tumor cells to escape from immune surveillance.Clinical success of the antibody drugs has proven that blockade of PD-1/PD-L1 pathway is a promising strategy for cancer immunotherapy.Here,we developed a cyclic peptide C8 by using Ph.D.-C7C phage display technology.C8 showed high binding affinity with hPD-1 and could effectively interfere the interaction of PD-1/PD-L1.Furthermore,C8 could stimulate CD8+ T cell activation in human peripheral blood mononuclear cells (PBMCs).We also observed that C8 could suppress tumor growth in CT26 and B16-OVA,as well as anti-PD-1 antibody resistant B 16 mouse model.CD8+ T cells infiltration significantly increased in tumor microenvironment,and IFN-γ secretion by CD8+ T cells in draining lymph nodes also increased.Simultaneously,we exploited T cells depletion models and confirmed that C8 exerted anti-tumor effects via activating CD8+ T cells dependent manner.The interaction model of C8 with hPD-1 was simulated and confirmed by alanine scanning.In conclusion,C8 shows anti-tumor capability by blockade of PD-1/PD-L1 interaction,and C8 may provide an alternative candidate for cancer immunotherapy.