Objective To analyze the clinical significance of serum pentraxin (PTX3), interleukin (IL-10), and heparin-binding protein (HBP) in the diagnosis of pulmonary tuberculosis (PTB). Methods 122 patients with PTB treated in a hospital from December 2018 to June 2021 were selected as the tuberculosis group, they were subdivided into cavity group and non-cavity group according to whether there was a pulmonary cavity; 113 patients who underwent physical examination in this hospital during the same period were selected as control group, and 109 patients with latent infection were selected as latent group. The expression levels of PTX3, IL-10, and HBP in different populations and with or without pulmonary cavity were compared; the expression levels of PTX3, IL-10, and HBP were compared between patients with and without cavity absorption after treatment; the expression levels of PTX3, IL-10, and HBP in patients with PTB after 1, 2 and 3 months treatment were compared, the value of PTX3, IL-10, and HBP in the diagnosis of PTB were analyzed. Results The expression levels of PTX3, IL-10, and HBP in tuberculosis group were all higher than those in latent infection group and control group, differences were all significant (all P < 0.05). The expression levels of PTX3, IL-10, and HBP in cavity group were all higher than those in non-cavity group, differences were all significant (all P < 0.001). After treatment, the expression levels of PTX3, IL-10, and HBP in the cavity absorption group were all lower than those in cavity non-absorption group (all P < 0.001). Levels of PTX3, IL-10, and HBP decreased gradually after treatment, levels of PTX3, IL-10, and HBP in patients with PTB at 3 months were all lower than those at 1 and 2 months after treatment (all P < 0.05). The area under the curve (AUC) of PTX3, IL-10, and HBP for the diagnosis of PTB were 0.756, 0.745 and 0.752 respectively, PTX3 was slightly higher than IL-10, and HBP, but there was no significant difference among the three (P > 0.05). Conclusion PTX3, IL-10, and HBP are highly expressed in patients with PTB, which is expected to become a reference indicator for the evaluation of disease condition of patients with PTB, and provide new ideas for clinical diagnosis and treatment.