Abstract: Objective To investigate the effect of CUE domain-containing protein 2 (CUEDC2) on the sensitivity of ovarian cancer cellstocisplatin and its mechanisms. Methods CUEDC2 gene in SKOV3 cells were knocked down by siRNA, and then MTS assay and Trypan blue staining technique were used to detect the effect of cisplatin on the cell proliferation of si-control group's (treated with si-control 50 nmol/L) and si-CUEDC2 group's (treated with si-CUEDC2 50 nmol/L) SKOV3 cells. SKOV3 cells were grouped into drug group (cisplatin 8μmol/L), si-control group (cisplatin 8μmol/L, si-control 50 nmol/L), si-CUEDC2 group (cisplatin 8μmol/L, si-CUEDC2 50 nmol/L), non-treatment group, and the expressions of related protein in MAPK were evaluated by western blotting. Results There was no significant difference in the quantity of SKOV3 cells between si-CUEDC2 without cisplatin treatment group and si-control group. Compared with si-control group, the quantity of SKOV3 cells decreased significantly in the si-CUEDC2 with cisplatin treatment group (P< 0.05). Under the effect of cisplatin, p38 phosphorylation level increased while p-ERK phosphorylation level decreased in SKOV3 cells with knockdown of CUEDC2. Conclusion Knocking down CUEDC2 can increase the sensitivity of SKOV3 cells to cisplatin, and CUEDC2 may play a role in regulating the effect of cisplatin on ovarian cancer cell proliferation through MAPK pathway.