Abstract: Objective To explore drug resistance of aneuploid colon cancer cells to cisplatin. Methods The HCT116 cells with expression of knockdown MAD2 induced by doxycycline(DOX)were designed as DOX(+)group(aneuploid), and HCT116 cells without process of DOX were designed as DOX(-)group(euploid). CCK-8 method was used to process cells in both groups, and CCK-8 test and cytometry were used to analyze the effect of cisplatin on cell growth. Quantitative real time polymerase chain reaction(qRT-PCR)was used to detect the expression of pro-apoptotic genes BAX, PUMA and NOXA in the cells. Results Cells were treated with cisplatin at different concentrations. CCK-8 test and cytometry showed that cells in DOX(+)group were more resistant to cisplatin than those in DOX(-)group. Western blot showed that the resistance of cells in DOX(+)group was related to the lower expression of apoptotic protein after cisplatin treatment. The qRT-PCR showed that the expressions of apoptosis gene PUMA, NOXA and BAX in DOX(+)group were significantly lower than those in DOX(-)group(P<0.05 or P<0.01)after process of cisplatin. Conclusion The aneuploid colon cancer cells are resistant to cisplatin treatment.