Objective To explore the effect of salubrinal (sal,an endoplasmic reticulum stress inhibitor) on radiosensitivity of human head and neck squamous carcinoma cells (HNSCC).Methods Cells were divided into two groups of sal treatment and its control.For drug treatment group,cells were treated with 10 mmol/L sal for different time (12,24,36 h) and then irradiated.The levels of a core protein GRP78 of endoplasmic reticulum stress (ERS) in HNSCC (KB,Fadu,and Detroit 562 cells)were analyzed by Western blot assay at different time (0,20 min,1 h,3 h,6 h,12 h,24 h and 48 h) after irradiation.Cell survival was measured with colony formation assay.Results Western blot assay revealed that the protein levels of GRP78 in three kinds of HNSCC significantly increased from 20 min to 1 h and peaked at 3 h after radiation (t =12.72,13.37,18.31,P ＜ 0.05).Compared with the control group,treatment of cells with sal decreased GRP78 protein levels (t =14.25,5.34,3.12,P ＜ 0.05) in three cell lines and also significantly enhanced radiation damage and reduced cell viability.The sensitization enhancement ratios (SER) of sal in three cell lines were 1.16,1.05 and 1.06,respectively.Conclusions Rradiosensitivity of HNSCC could be effectively enhanced by sal treatment.