Abstract: Objective To investigate the effect of recombinant fusion protein TAT-OSBP-MKK6（E）on the proliferation，invasion and metastasis of cisplatin（DDP）-resistant human epithelial ovarian cancer cell SKOV3／DDP. Methods MTT assay was used to analyze the influence of TAT-OSBP-MKK6（E）alone or in combination with a autophagy inhibitor 3-methyladenine（3-MA） on the sensitivity of DDP in SKOV3／DDP cells.The autophagy level was observed by monodansylcadaverin staining. The mRNA and protein expression levels of Beclin 1 were evaluated by QPCR and Western blotting after challenge with fusion protein. The abilities of invasion and migration were evaluated by Transwell assay. Results The half-inhibition concentration（IC50）of SKOV3／DDP cells was（37.62±2.63）μg／ml. After being exposure to 10，20 and 40 μg／ml fusion protein，the IC50 of SKOV3／DDP cells was decreased to（17.07± 0.88），（11.08 ±0.57）and（1.96±0.31）μg／ml，respectively（P＜0.001）. The inhibition of autophagy by 3-MA abolished the sensitivity of SKOV3／DDP cells to DDP induced by TAT-OSBP-MKK6（E）. The autophagy fluorescence of SKOV3／DDP in the group of TATOSBPMKK6（E） and TATOSBPMKK6（E）plus 3-MA were 824±107 and 459±128，higher than 306±143 of control group（P＜0.05）. The mRNA and protein expression levels of Beclin 1 elevated with the increase of TAT-OSBP-MKK6（E） concentration（10, 20, 40 μg/ml），and the differences between each concentration group and control group were statistically significant（P＜0.01）. The expression of Beclin 1 protein in SKOV3／DDP cells was also different among control group， TATOSBPMKK6（E）group and DDP plus TAT-OSBP-MKK6（E）group（P＜0.05）. The expression of Belin1 protein were the highest in the TAT-OSBP-MKK6（E）plus DDP group（0.876±0023） followed by that of TAT-OSBP-MKK6（E）group（0.564±0.021）. Cell migration and invasion assay showed that TAT-OSBPMKK6（E）could inhibit the invasion and migration ability of SKOV3／DDP cells，and the difference of TAT-OSBP-MKK6（E）plus DDP group and TAT-OSBP-MKK6（E） group were significant compared with control group（P＜0.05）. No significance was observed between DDP group and control group（P＞0.05）. Conclusion Recombinant fusion protein TAT-OSBP-MKK6（E）can effectively inhibit the proliferation，invasion and migration of SKOV3／DDP cells，probably by inducing autophagy and up-regulating Beclin 1 expression.