Objective To investigate the clinical efficacy and mechanism of modified Yiyifuzibaijiang granules in the treatment with acute milk moth of lung-stomach hyperthermia type. Methods 80 patients with acute milk moth of lung-stomach hyperthermia type were selected and randomly divided into observation group and control group, 40 cases in each group. Observation group was given oral treatment with modified Yiyifuzibaijiang granules; The control group was given ampicillin capsules orally. After 7 days of treatment, the main symptoms such as sore throat, swollen tonsils and suppuration, and the minor symptoms such as fever, cough, thirst, irritability, tongue coating and stool were scored before and after treatment in both groups, so as to observe the clinical efficacy of modified Yiyifuzibaijiang granules. Serum interleukin-1β(IL-1β) was detected by Elisa kit before and after treatment. NLRP3 mRNA and caspase-1 mRNA were detected by polymerase chain reaction(PCR) to objectively reflect the inflammatory status of patients. Adverse reactions were recorded. Results It was statistically significant that the clinical effective rate of the observation group was 91.89% and the control group was 72.22% after 7 days of treatment. Treatment significantly improved both main symptoms and secondary symptoms in both groups(P<0.05), with the observation group outperforming the control group(P<0.05). Both treatments could significantly down-regulate the expression of NLRP3 mRNA, caspase-1 mRNA and IL-1β in serum of the children (P<0.05). No adverse reactions occurred in the observation group, while vomiting occurred in 1 case and diarrhea occurred in 3 cases in the control group. Conclusion Modified Yiyifuzibaijiang granules can effectively treat acute milk moth of lung-stomach hyperthermia type by regulating NLRP3 signaling pathway, and there is no adverse reaction.