Abstract: Objective To investigate the changes in sensitivity to anthracycline and taxanes of human breast cancer cells after RABEX-5 downregulated. Methods By constructing a lentiviral vector for RNA interference (RNAi) of RABEX-5 gene and transfected into human breast cancer cell line MCF-7 to silence the express of RABEX-5. Real-time PCR and Western blot were used to detect the silencing effect. The changes in sensitivity to chemotherapeutic drugs of MCF-7/RNAi and its negative control cell lines MCF-7/vector were detected by CCK-8 reagent. Results Compared with MCF-7 cell and MCF-7/vector cell, the expression of RABEX-5 mRNA and protein was downregulated in MCF-7/RNAi cells. The sensitivity to epirubicin was reduced after downregulating the expression of RABEX-5, the 50% inhibition concentration (IC50) of MCF-7/RNAi 〔(3.590 0±0.228 69) μg/mL〕 was higher than that of MCF-7/Vvector 〔(1.193 3±0.187 71) μg/mL, P50 were (11.162 7±0.210 26) μg/mL and (10.536 7±0.430 97) μg/mL, respectively (P>0.05). Conclusion Downregulation of RABEX-5 can induce chemoresistance to epirubicin in human breast cancer cell MCF-7; while its effect on sensitivity to docetaxel is not significant. This study can provide a theoretical basis for future research RABEX-5 in the individualized treatment of breast cancer.