To clarify clinical significance of high mobility group box 1 level in inflammation of asthma-chronic obstructive pulmonary disease overlap syndrome. A total of 124 asthma patients in acute attack (asthma group), 124 chronic obstructive pulmonary disease patients in acute exacerbation (chronic obstructive pulmonary disease group) and 124 asthma-chronic obstructive pulmonary disease overlap syndrome patients in acute exacerbation (asthma-chronic obstructive pulmonary disease overlap syndrome group) hospitalized in the department of geriatric respiratory medicine and the second department of respiratory medicine of our hospital from January 2020 to June 2022 were enrolled. The C-reactive protein level, white blood cell counts and high mobility group box 1 concentration were measured and compared in three groups. The relation of serum high mobility group box 1 level to C-reactive protein level or white blood cell counts was assessed through Pearson correlation. The relation of serum high mobility group box 1 level to forced expiratory volume 1 % predicted or forced expiratory volume 1/forced vital capacity was assessed through Pearson correlation. The general data presented no difference among three groups (p>0.05). The C-reactive protein level, white blood cell counts and high mobility group box 1 concentration of asthma-chronic obstructive pulmonary disease overlap syndrome patients presented elevation relative to those of asthma patients and chronic obstructive pulmonary disease patients (p<0.05). The serum high mobility group box 1 level presented a positive association with C-reactive protein level or white blood cell counts in asthma-chronic obstructive pulmonary disease overlap syndrome group (p<0.05). The serum high mobility group box 1 level presented a negative association with forced expiratory volume 1 % predicted or forced expiratory volume 1/forced vital capacity in asthma-chronic obstructive pulmonary disease overlap syndrome group (p<0.05). High mobility group box 1 level in blood specimens of asthma-chronic obstructive pulmonary disease overlap syndrome patient’s presents a marked elevation, suggesting that high mobility group box 1 has crucial clinical significance in diagnosis and therapy of asthma-chronic obstructive pulmonary disease overlap syndrome.