Objective：To investigate the effects and mechanism of PLOD2 on oxaliplatin chemoresistance in ovarian cancer. Methods：A2780 cells and OV1063 cells were infected with the lentivirus encoding shRNA against PLOD2 or lentivirus encoding OERNA against PLOD2 respectively. The stably transfected cell lines were selected by puromycin. The expression levels of PLOD2 were detected by qRT⁃PCR and Western blot. CCK⁃8 proliferation test，clone formation assay and flow cytometry were used to detect effects of oxaliplatin on cell proliferation and apoptosis. The xenograft nude mouse tumor model was used to observe inhibition effect of oxaliplatin on tumor growth after PLOD2 downregulation；The mRNA and protein expressions of BCRP and MRP1 were detected by qRT ⁃ PCR and Western blot. Results：The mRNA and protein expressions of shPLOD2(transfected with PLOD2 shRNA)and OEPLOD2(transfected with PLOD2 OERNA)were significantly lower or higher compared with the control groups(transfected with the scrambled shRNA or OERNA). At the same concentration of oxaliplatin，the shPLOD2 group showed higher proliferation inhibition rate，the IC50 value of the shPLOD2 was lower，the ability of clone formation of shPLOD2 group decreased significantly，and the apoptosis rate increased significantly than those in the control group. In contrast，at the same concentration of oxaliplatin，the OEPLOD2 group showed lower proliferation inhibition rate，the IC50 value of the OEPLOD2 was higher，the ability of clone formation of OEPLOD2 group increased significantly，and the apoptosis rate decreased significantly than those in the control group. Compared withthe shControl group，the volume and weight of transplanted tumors in the shPLOD2 group under oxaliplatin treatment were significantly decreased. The mRNA and protein expressions of chemoresistance ⁃ related gene BCRP and MRP1 decreased after interference with PLOD2 expression. However，the mRNA and protein expressions of chemoresistance ⁃ related gene BCRP and MRP1 increased after PLOD2 overexpression. Conclusion：The study suggests that PLOD2 can intensify the oxaliplatin chemoresistance of ovarian cancer， which may be related to the upregulation of BCRP and MRP1 expression.