Objectives: To investigate whether the levels of interleukin 1 beta (IL-1 beta), interferon. (IFN-.), tumor necrosis factor a (TNF-a) in children with Kawasaki disease (KD) are correlated with coronary artery lesion (CAL) and resistance to intravenous immunoglobulin (IVIG) treatment. Methods: A total of 216 children in line with KD diagnostic criteria were continuously included as subjects, and 50 healthy children at the same period were selected as the control group, and their levels of IL-1 beta, IFN-., and TNF-a were detected. Results: Subjects were subdivided according to the presence or absence of CAL: 42 cases (19.4%) of 216 children with KD developed CAL and were subdivided into the CAL group, while 174 (80.6%) of those who did not develop CAL were subdivided into the NCAL group. The levels of IL-1 beta, IFN-., and TNF-a in the CAL group and the NCAL group were higher than those in the control group (P<0.05), and the levels of those in the CAL group were higher than those in the NCAL group (P<0.05). Subjects were subdivided according to the effect of IVIG treatment: 194 cases (89.8%) of 216 children with KD had a good control of inflammation after the initial IVIG treatment, and were considered to have IVIG-sensitive KD and divided into the IVIG-sensitive group; 22 cases (10.2%) could not get good control of inflammation after the initial IVIG treatment, and were considered to have IVIG-resistant KD and divided into the IVIG-resistant group. The levels of IL-1 beta, IFN-., and TNF-a in the IVIG-sensitive group and the IVIG-resistant group were higher than those in the control group; The levels of IL-1 beta, IFN-., and TNF-a in the IVIG-resistant group were higher than those in the IVIG-sensitive group (P<0.05), while the fever time of the IVIG-sensitive group was lower than that of the IVIG-resistant group (P<0.05). Conclusion: Children with KD may experience changes in IL-1 beta, IFN-., and TNF-a levels in the acute phase. Such a significant increase in levels may be a risk factor for CAL and resistance to IVIG treatment in children with KD, while the prolonged fever time is a risk factor for resistance to IVIG treatment in children with KD.