Objective To investigate the effects of human papilloma virus 16 E6 (HPV16 E6) on endoplasmic reticulum (ER) stress-autophagic response in the cervical cancer C33A cells.Methods Polymerase chain reaction was used for detecting the integration of HPV DNA.The eukaryotic expression vector of HPV16 E6 was constructed and transfected via lipofectamine into C33A cells.Experimental cells were classified into 3 groups:pcDNA3.1--HPV16 E6 group,pcDNA 3.1-group and C33A group.Western blot was used to measure expression of protein of HPV16 E6,Beclin 1,LC3 Ⅱ,IRE1,PERK and ATF6 in transfected cells.Results here was no HPV DNA integration in C33A cells that were confirmed as the intervention cells.Eukaryotic expression vector pcDNA3.1--HPV16 E6 was constructed successfully.The eukaryotic expression vector pcDNA3.1--HPV16 E6 significantly improved the expression of protein of HPV 16 E6 in C33A cells.The protein expression of Beclin 1,LC3 Ⅱ,IRE1,PERK and ATF6 were significantly improved after transfection with vector pcDNA3.1 +-HPV16 E6 (P ＜ 0.05).Furthermore,LC3 Ⅱ protein level was reduced by treatment with ER stress inhibitor.Conclusion HPV16 E6 can improve autophagy through the ER stress pathway,and this response may play an important role in the process of HPV16 E6 inducing cervical cancer,providing one of the new strategies for gene therapy of cervical carcinoma.