Objective To analyze the drug resistance and related factors of smear-positive tuberculosis cases. Methods We collected the relevant information and sputum specimens of patients which were positive sputum smear microscopy in Shou county from 2013 to 2016, and then conducted the bacterial culture, drug sensitivity testing and strain identification. Results A total of 242 cases of smear positive pulmonary tuberculosis were investigated, including 239 cases of mycobacterium tuberculosis infection (98.8%) and 3 cases of non tuberculous mycobacterium infection(1.2%). Among the 239 patients with mycobacterium tuberculosis, the overall drug resistance rate was 28.9%, the mono-resistance rate was 14.2%, MDR-TB rate was 5.9%, the poly-resistance rate was 5.9%, and the XDR-TB rate was 2.9%. The first four drugs with high drug resistance rate were isoniazid (INH) 15.5%, streptomycin (SM) 15.5%, rifampin (RFP) 13.4% and OFX 7.1%. 195 cases (81.6%) were initially treated, 44 cases (18.4%) were retreated. The drug resistance rate of newly diagnosed patients was 21.5%, the resistance rate of retreated patients was 61.4%, and the difference was statistically significant. The multifactor logistic regression analysis showed that the compound was an independent risk factor for total resistance, multidrug resistance and extensive resistance. Conclusion The drug resistance situation was still grim in Shou county, especially in recurrent tuberculosis patients who have higher drug resistance rate. Therefore, we should further standardize the TB treatment and management, strengthen the resistant monitoring work, and guide the clinical medication.