Abstract: Objective To explore the effects of Cisplatin(DDP) and 5-fluorouracil(5-Fu) on the expression of NKG2D ligands of human esophagus carcinoma cell EC9706 and cytokine-induced killer (CIK) cells cytotoxicity. Methods The IC₅₀ of DDP,5-Fu against EC9706 cells were measured by MTT assay.Expressions of signal pathway molecules involved in DNA damage and repair system were detected by RT-PCR.The expression of NKG2D ligands (MICA,MICB,ULBP1,ULBP2,ULBP3) were analyzed by flow cytometery.Cytotoxicities of CIK cells against EC9706 cells before and after cultured by 1/2 IC₅₀ DDP or 5-Fu were analyzed by LDH releasing assay at effector-to-target cell ratio(E∶T) of 20∶1. Results DDP,5-Fu could decrease the proliferation and survival rate of EC9706 cells,the IC₅₀ was 5 μg/ml and 10 μg/ml,respectively,which increased mRNA expressions of signal pathway molecules involved in DNA damage and repair system.MICA,MICB,ULBP2,ULBP3 on EC9706 cells were over expressed after 72 h cultured with 1/2 IC₅₀ DDP,while expression of MICA,ULBP2,ULBP3 were higher after treated by 1/2 IC50 5-Fu.Cytotoxicity of CIK cells against EC9706 cells cultured by 1/2 IC50 DDP,1/2 IC50 5-Fu were（37.08±0.62）%,（59.33±2.10）%,（52.44±0.97）%,respectively.Cytotoxicity of CIK cells against EC9706 cells cultured by either 1/2 IC50 DDP or 1/2 IC₅₀ 5-Fu was significantly enhanced. Conclusion The results indicate that DDP or 5-Fu can enhance the susceptibility of EC9706 cells to CIK cells-mediated killing effect by upregulating the expressions of NKG2D ligands through activating signal pathway molecules involved in DNA damage and repair system.