There is considerable inter-individual variability in chemoradiotherapy responses in nasopharyngeal carcinoma (NPC) patients receiving the same or similar treatment protocols.In this study we evaluated the association between the gene polymorphisms in endoplasmic reticulum (ER) stress pathway and chemoradiation responses in Chinese NPC patients.A total of 150 patients with histopathologically conformed NPC and treated with concurrent chemoradiotherapy were enrolled.Genotypes in ER stress pathway genes,including VCP (valosin-containing protein) rs2074549,HSP9OB1 rs17034943,CANX (calnexin) rs7566,HSPA5 [heat shock protein family A (Hsp70) member 5] rs430397,CALCR (calcitonin receptor) rs2528521,and XBP1 (X-box binding protein 1) rs2269577 were analyzed by Sequenom MassARRAY system.The short-term effects of primary tumor and lymph node after radiotherapy were assessed based on the Response Evaluation Criteria in Solid Tumors (RECIST) of WHO.And acute radiation-induced toxic reactions were evaluated according to the Radiation Therapy Oncology Group or European Organization for Research and Treatment of Cancer (RTOG/EORTC).The effects of gene polymorphisms on clinical outcomes of chemoradiotherapy were assessed by chi-square test,univariate and multivariate logistic regression analyses.We found that CT and CT+CC genotypes of CANX rs7566 was significantly correlated with primary tumor treatment efficacy at 3 months after chemoradiotherapy and with occurrence of radiation-induced myelosuppression in Chinese NPC patients.CT and CT+CC genotypes of CALCR rs2528521 were significantly correlated with cervical lymph node efficacy at 3 months after chemoradiotherapy.And CC and CT+CC genotypes of VCP rs2074549 were significantly associated with occurrence of myelosuppression.In conclusion,SNPs of VCP rs2074549,CANX rs7566 and CALCR rs2528521 in ER stress pathway genes may serve as predictors for clinical outcomes of chemoradiotherapy in Chinese NPC patients.