Abstract: Objective To investigate the correlations of interleukin-1β (IL-1β) level and percentage of CD16⁺CD56⁺ natural killer (NK) cells in peripheral blood with severity of disease in patients with pulmonary tuberculosis. Methods A total of 150 patients with active pulmonary tuberculosis (APTB) in the Suqian First People′s Hospital from January 1, 2021 to September 1, 2023 were selected as APTB group, and 150 patients with inactive pulmonary tuberculosis (IPTB) in the same period were selected as IPTB group. Level of IL-1β and percentage of CD16⁺CD56⁺ NK cells in peripheral blood of patients with different disease severities were compared, and their correlations with severity of disease were analyzed. Results In the APTB group, level of IL-1β in the peripheral blood was significantly higher than that in the IPTB group, while the percentage of CD16⁺CD56⁺ NK cells was significantly lower (P < 0.001). In the mild, moderate, and severe groups, level of IL-1β showed a significant gradual increasing trend in peripheral blood, while the percentage of CD16⁺CD56⁺ NK cells showed a significant gradual decreasing trend (P < 0.001). After treatment, the level of IL-1β in the peripheral blood decreased significantly, while the percentage of CD16⁺CD56⁺ NK cells increased significantly in the APTB group (P < 0.001). Correlation analysis revealed that level of IL-1β in the peripheral blood of patients with pulmonary tuberculosis was positively correlated with severity of disease (r=0.732, P < 0.001), while the percentage of CD16⁺CD56⁺ NK cells was negatively correlated with severity of disease (r=-0.612, P < 0.001). Conclusion Level of IL-1β in the peripheral blood is elevated while the percentage of CD16⁺CD56⁺ NK cells is decreased in patients with pulmonary tuberculosis, which is closely related to the severity of APTB.