Abstract: Background and Objective: All living organisms could be exposed to Benzo[a]pyrene (BaP) that resulted mainly from burning of industrial carbon compounds, volcanic eruptions and forest fires causing genotoxic and carcinogenic effects. The current study aimed to examine the protective role of Echinacea purpurea (E. purpurea) against BaP-induced genotoxicity and biochemical damage in mice. Materials and Methods: Eight experimental groups were designed. Group 1: Negative control, group 2 received single dose of BaP (200 mg kg–1 b.wt.), groups 3-5 received the same dose of BaP but pretreated orally with E. purpurea (100 mg kg–1 b.wt.) for 1, 7 and 14 days respectively, groups 6-8 received oral dose of E. purpurea for 1, 7 and 14 days, respectively. Chromosomal abnormalities, DNA fragmentation and gene expression of CYP1A2, CYP3A4 and GR genes were assessed in the liver. Lipid peroxidation and antioxidant enzyme activities were evaluated in mice. Results: Significant reduction (p<0.01) in chromosomal abnormalities induced by BaP was observed in animals pretreated with E. purpurea for 7 and 14 days. In liver cells, the inhibition percent of DNA fragmentation reached 37.6 and 60.4% respectively. In bone marrow, the inhibition percent of cells with comet tail reached 32.7 and 54.8%, respectively. Mice treated with E. purpurea combined with BaP showed significant increase (p<0.05) in gene expression of CYP1A2, CYP3A4 and GR in liver cells through the experimental periods. Significant stimulation of antioxidants (GST, catalase and reduced glutathione) was observed in E. purpurea treated animals. Pretreatment with E. purpurea significantly reduced lipid peroxidation induced by BaP in liver and kidney. Conclusion: The E. purpurea might help in relief the deleterious consequence of carcinogens as BaP.