Objective The endoplasmic reticulum (ER) is an essential site of cellular homeostasis regulation.ER stress can induce autophagy in tumor cells escaping from apoptosis.In this study, we examined the effect and mechanism of endoplasmic reticulum stress on cisplatin sensitivity in ovarian carcinoma.Methods Tumor cells SKOV3 being treated with saquinavir were subjected to Western Blot and RT-PCR to determine protein and mRNA expression levels of mTOR and Beclin1.MTT assay was used to analyze influence of saquinavir on cisplatin resistance in SKOV3 cells.Results Saquinavai could induced GRP78 expression, which was a marker of ER stress.After induced by different doses of Saquinavair, the sensitivity of ovarian cancer cells to cisplatin was decreased significantly.The protein and mRNA expression levels of mTOR and Beclinl in SKOV3 cells were increased when the cells were exposed to Saquinavair or DDP for 24h.Moreover, their expression were highest in group of (Saquinavair + DDP), which were (0.684 ± 0.072)and(0.6467±0.0468),respectively.We also observed tumor cells SKOV3 were exposed to the autophagy inhibitor 3-MA and different concentrations of Saquinavai, which IC50 values of DDP were decreased compared with Saquinavai alone(P<0.001), suggesting that the sensitivity to cisplatin was improved in ovarian cancer cells after 3-MA exposure.Conclusions Saquinavir can induce cell SKOV3 ER stress effectively.Induced-endoplasmic reticulum stress can decrease the sensitivity of cisplatin in SKOV3.Endoplasmic reticulum stress could regulate autophagy of cell through the mTOR and Beclin1 pathways, leading to reduce the sensitivity of cisplatin in SKOV3.ER stress of tumor cells and autophagy could be the target to improve therapeutic effect in chemotherapy and to deteriorate drug resistance in tumor.