Abstract: Objective To understand the polymorphism of antigens PE 35 and PPE 68 genes of Mycobacterium tuberculosis and evaluate the influence of the polymorphism on immune recognition. Methods A total of 161 clinical M. tuberculosis strains isolated in China were selected and comparative sequence analysis of PE 35 and PPE 68 genes was conducted after amplification. Results Among the 161 M. tuberculosis strains, 23 showed the polymorphism in the gene sequence of PE 35 and 8 showed the polymorphisms in the gene sequence of PPE 68. The mutations in all the PE 35 gene, except that in JL06018, influenced the T cell epitopes. In PPE 68 gene, 58 of 62 T cell epitopes changed, accounting for 93.5%. The mutation rate of PE 35 gene in non-Beijing family strains was significantly higher than that in Beijing family strains (P0.05). Although the mutation rate of PPE 68 gene in non-Beijing family strains was higher than that in Beijing family strains, the difference had no statistical significance. Conclusion Polymorphisms were observed in PE 35 and PPE 68 genes, which might resulting in the drastic changes in the functions of these proteins and influence the virulence of the strains. Beijing family strains are more likely to be recognized than non-Beijing family strains by host T cell in PE 35 gene, which facilitates the spread of Beijing family strains.