To explore the effect of konjac glucomannan (KGM) on genomic stability in colonic epithelial cells, the normal colon cell line NCM460 and the colonic cancer cell lines SW620 and HCT116 were used as the research materials. The tested cells were treated with KGM at concentrations of 0, 0.625, 0.625, 2.5,5, 10, 20, and 40 mg/mL for 24, 48, and 72 h. Cell viability was detected by methylthiazolyldiphenyl-tetrazolium bromide(MTT) assay. The CBMN-Cyt assay was performed to detect the genome instability (GIN), nuclear division index (NDI), and apoptosis levels in the tested cells after treatment with different concentrations of KGM (5, 20, and 30 mg/mL) for 72 h. The results showed that after 72 h of treatment with different concentrations of KGM, the viability of NCM460 cells increased significantly(P<0.05) within 5~40 mg/mL, while their GIN significantly decreased(P<0.001) at 5 mg/mL KGM and significantly increased at 30 mg/mL(P<0.01). The viability of HCT116 cells was significantly inhibited by KGM at concentrations of 5~40 mg/mL (P<0.05), while KGM at a concentration of 40 mg/mL exhibited an extremely pronounced inhibitory effect on the viability of SW620 cells(P<0.01). Moreover, GIN and apoptosis rate of SW620 and HCT11 cells significantly increased at KGM concentrations of 5~30 mg/mL(P<0.001), while NDI reduced significantly(P<0.05). The results suggest that low concentration(5 mg/mL) of KGM is beneficial to maintain the genomic stability in normal epithelial cell NCM460, and various concentrations(5~30 mg/mL) of KGM increases GIN and apoptosis rate in the colon cancer cells SW620 and HCT116, which may provide a molecular basis for maintaining intestinal health.