Objective：To investigate the effects of trophoblast cell-surface antigen 2（Trop2）on drug resistance of gastric cancer and the underlying mechanism. Methods：BGC823 cells were infected with the lentivirus encoding shRNA against Trop2 and puromycin was used to select stable cell lines；The effects of interference were detected by qRT-PCR，Western blot and immunofluorescence；CCK-8 proliferation test and flow cytometric detection were performed to detect the influence of daunorubicin on cell proliferation and apoptosis. The mRNA and protein expressions of TopoⅡα were detected by qRT-PCR and Western blot. Results：The mRNA and protein expressions of Trop2 in the shTrop2 group（transfected with Trop2 shRNA）were significantly lower than those in the control group（untreated）and the shNC group（transfected with normal control shRNA）；The shTrop2 group showed higher proliferation inhibition rates after daunorubicin treatment than these in the control group and the shNC group，and the IC50 value of the shTrop2 group was lower than that in the control group and the shNC group（P＜0.05）；The daunorubicin-induced cell apoptosis rate in the shTrop2 group was higher than that in the control group and the shNC group（P＜0.05）；The mRNA and protein expressions of drug resistance-related gene TopoⅡα decreased after interference with Trop2 expression stably. Conclusion：Trop2 can intensify daunorubicin resistance of gastric cancer cells by inhibiting the expression of TopoⅡα.