Abstract： Objective To evaluate the effect of replication protein A (RPA) gene suppression on the radiosensitivity of esophageal cancer cells (TE-1R ) and underlying mechanism. Methods A radioresistant human esophageal cancer cell line TE-1 R was screened out by fractionated irradiation to TE-1 cells,then siRPA1 or siRPa2 was transfected to TE-1R cells.The untransfected (Con) group and nonsense siRNA transfected (NC) group were set as control groups.The survival was measured with colony-forming assay and the cell cycle distribution was measured with flow eytometry.Results Compared with the Con and NC groups,the protein expression of RPA1 and RPA2 decreased significantly 48 h after siRPA1 and siRPA2 transfection.The D0,Dq,and SF2 values reduced from 2.09,1.70,0.85 in NC group to 1.67,0.71,0.44 and 1.82,0.89,0.51 in siRPAl and siRPA2 transfection groups,respectively.Accordingly,the sensitization enhancement ratios of Dq were 2.39 and 1.91,respectively.The G2/M arrest in siRPA1 and siRPA2 transfection groups increased from (18.701 3.14)％ of NC group to (26.95 ± 3.96)％ and (25.28 ± 2.74) ％ (t =2.827,2.853,P ＜0.05),respectively.Conclusions Knocking down of RPA1 or RPA2 genes can enhance the raidosensitivity of human esophageal cancer cells TE-1R,where the inhibition of radiation-induced sublethal damage repair may be involved.Accordingly,RPA may become a new target of radiosensitization in esophageal cancer.