Objective To clarify the relationship between different species of Mycobacterium avium complex（MAC），drug sensitivity and clinical prognosis in Guangzhou. Methods The clinical isolates of MAC from 2018 to 2020 were collected from the Mycobacterium Strain Bank in Guangzhou，and the MAC strains of MAC lung disease patients were sequenced to identify them by 16S rRNA，ITS，rpoB，hsp65 multi⁃target gene sequencing. MIC50 and MIC90 of its minimum inhibitory concentration（MIC）were determined by microplate method to deter⁃ mine its drug sensitivity. The success of clinical treatment can be judged according to the clinical symptoms，DR/ CT radiology and pathogen culture results. Results （1）There were 67 strains of Mycobacterium intracellulare （73.63%）and 21 strains of Mycobacterium avium（23.08%）in 91 clinical isolates of MAC.（2）The resistance rates of Mycobacterium avium and Mycobacterium intracellular to amikacin and ethambutol were different（P < 0.05）.（3）There was significant difference in the treatment success rate between M.aviumpulmonary disease and M.intracellularepulmonary disease（66.67% vs. 41.27%，χ2 = 6.053，P < 0.05）. Conclusion M.intracellulare and M.avium were the main clinical isolates of MAC in Guangzhou，and there were differences in drug resistance and clinical prognosis among different MAC species. For patients with NTM pulmonary disease，strain identification and in vitro drug susceptibility tests should be conducted，and clinical treatment protocols should be formulated and optimized based on the above results.