Abstract: In order to study the toxicity of 4-methylnitrosamine-1-(3-pyridyl)-1-butanone (NNK) to mice and its relationship with Prx (peroxiredoxin) gene expression, experimental mice were exposed to NNK via intraperitoneal injection (2.5 and 5.0 mg/kg). After 24 weeks, HE (hematoxylin-eosin) staining and qRT-PCR (quantitative real-time polymerase chain reaction) were used to measure the toxicity of NNK on the lung, liver, kidney and testis of the treated mice and NNK's effect on the expression of Prx family genes. The results showed that: 1) Compared with the control group, the mice in the treatment group were more aggressive and had no significant change in food intake, however their body weight decreased five weeks after the exposure. 2) The mice in the treatment group had hyperplasia in alveolar septum, enlargement in hepatic sinuses and nuclei, hyaline degeneration and fragmentation of glomeruli, and decrease of spermatocytes in testicular seminiferous tubules. 3) Under the NNK stress, Prx genes were induced. The Prx gene expression differed in different tissues, the highest expression in the liver tissue was 34.8 times higher than that of the control mice. 4) In the control group, the Prx5 gene expression was lower, while it increased after the NNK treatment, especially at 5.0 mg/kg NNK treatment. Therefore, it is suggested that Prx5 gene might play an important role in anti-oxidation action under NNK stress.