Objective: To investigate the changes of serum tumor markers carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125) and carbohydrate antigen 199 (CA199) in patients with pulmonary tuberculosis and their clinical value. Methods: A total of 112 patients with pulmonary tuberculosis (pulmonary tuberculosis), 30 patients with lung cancer (the lung cancer group) and 30 healthy subjects (the control group) were selected. The serum tumor markers CEA, CA125 and CA199 were detected and compared. The diagnostic value of three tumor markers in tuberculosis were analyzed. Results: The levels of serum CEA, CA125 and CA199 in each group were significantly different (all P<0.05). The levels of serum CEA and CA199 in lung cancer group were significantly higher than those in tuberculosis group and control group (all P<0.05). The serum CA125 level in tuberculosis group was significantly higher than that in lung cancer group and control group (all P<0.01); the level of CA199 in lung cancer group was significantly higher than that in the control group (all P<0.05). The area under the ROC curve (AUC) of serum CA125 was 0.745 (95% CI: 0.711 to 0.861, P<0.001) with a sensitivity of 81.8% and a specificity of 62.3%. The combined detection of each tumor marker showed an AUC value of 0.776 (95% CI: 0.703 to 0.849, P<0.001) with a sensitivity of 85.6% and a specificity of 65.3%. Conclusion: Serum CA125 can be used as an important differential diagnosis index for tuberculosis. Combined detection of CEA, CA125 and CA199 can significantly improve the sensitivity of tuberculosis diagnosis.