Objective To study the effects of resistance to other anti ⁃tuberculosis drugs on mutations of isoniazid resistance related genes in M.tuberculosis for further accurately understanding the molecular mechanism of isoniazid resistance in M.tuberculosis. Methods The M.tuberculosis isolates which have complete drug sensitivity test（DST）data of eleven kinds of anti⁃tuberculosis drugs（isoniazid，rifampicin，ethambutol，streptomycin，amika⁃ cin，clarithromycin，levofloxacin，moxifloxacin，rifambdin，propylthioisonicotinamide and p⁃aminosalicylic acid） were were sampled from the bio⁃bank of Mycobacteria in Guangzhou. Then their katG，mabA⁃inhA，oxyR⁃ahpC， kasA and ndh genes were sequenced，and gene mutations were analyzed by comparing with the sequences of these genes of M.tuberculosis reference strain H37Rv.Statistical comparative analysis of the total gene mutation frequen⁃ cies of five genes between bacterial florae of H（- R/F/O）- and H（- R/F/O）+ ，H+ R- and H+ R+ ，H+ F- and H+ F+ ，and H+ O- and H+ O+ resistant phenotypes were performed by using Chi⁃square test（Among them，“R”，“H”，“F”，“O”， “+”and“-”represent rifampicin，isoniazid，Levofloxacin or moxifloxacin and seven kinds of other drugs，drug⁃ resistance and drug⁃susceptibility respectively. Results The first，the total gene mutation frequency of five genes in M.tuberculosis strains with H- （R/F/O）- was 11.32%（12/106）while the frequency was 40.54%（15/37）in M.tuberculosis strains with H- （R/F/O）+ among 143 isoniazid ⁃sensitive mycobacterium tuberculosis strains，which there was significant differences between them（χ2 = 15.289，P ˂ 0.001）. The second，the total gene mutation frequency of five genes in M.tuberculosis strains with H+ R- ，H+ R+ ，H+ F- ，H+ F+ ，H+ O- and H+ O+ were 47.87%（45/ 94），93.85%（122/130），68.64%（116/169），89.09%（49/55），55.56%（15/27）and 77.16%（152/197）. There were significant differences between M.tuberculosis strains with H+ R- and H+ R+ ，H+ F- and H+ F+ ，H+ O- and H+ O+ based on their chi⁃square values of 60.778，11.99 and 5.841 and P values of ˂ 0.001，0.001 and 0.016， respectively. Conclusions It is essential that important effects on isoniazid resistance related genes mutations in M.tuberculosis from other anti ⁃ tuberculosis drugs resistance should be studied extensively and deeply although these mutations were usually decided by their sensitivity to isoniazid.