Tuftsin, a naturally occurring tetrapeptide with a sequence Thr-Lys-Pro-Arg was evaluated for its in vivo protective effect against cyclophosphamide-induced genotoxicity and oxidative stress in Swiss albino mice. The anticancer drug cyclophosphamide (CP) was administered intra-peritonially to induce mutagenic effect. The drug treatment caused significant increase in chromosomal aberrations, formation of micronucleated polychromatic erythrocytes (MNPCE's), as well as oxidative stress and decrease in lipid peroxidation in liver of the animals. The pretreatment with tuftsin abolished such effects in dose-dependent manner and also increased mitotic index in the experimental animals. Results of the present study validated chemo-preventive properties of tuftsin against CP-induced chromosomal mutations and cellular injury of liver by oxidative stress.