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Objective: To study the preventive effect of Total Codonopsis lanceolata Saponin (CLS) on the damage of liver cell DNA induced by diethylnitrosamine (DEN), and provide the reference data for chemistry prevention of liver cancer.Methods: Fifty mice were randomly divided into five groups, negative control group (taken distilled water by intragastric administration), DEN group (taken DEN 20mg/kg by Intraperitoneal injection every other day), high, middle and low dose groups (taken CLS 200, 100 and 50mg/kg by intragastric administration every day, taken DEN 20mg/kg by Intraperitoneal injection every other day), and treated for 6 weeks.DNA damages of liver cells were analyzed by single cell gel electrophoresis technique, the contents of malondialdehyde (MDA), the activities of Glutathione peroxidase (GSH-Px) and superoxidedismutase (SOD) in liver tissue were determined by colorimentry.Results: CLS has no significant improvement for mice weight growing inhibiting.Comet tail length, comet length, tail moment, Olive tail moment and tail DNA% of three CLS dose groups were significantly lower than that of DEN group(P<0.05), DNA damage degree of each CLS dose group was significantly lower than that of DEN group(P<0.05).SOD activity of CLS high dose group was significantly higher than that of DEN group(P<0.01), GSH-Px activities of CLS high and middle groups were significantly higher than that of DEN group(P< 0.01), the contents of MDA in three CLS dose groups were significantly decreased than that of DEN group with dose-dependent reduction(P<0.01).Conclusion: Codonopsis Ianceolata saponin has some protective effects on the DNA damage of liver cell induced by DEN in mice.