<ins> Objective:</ins><ins> To explore the clinical effect of modified Chaihu Jia Longgu Muli Decoction combined with Wendan Decoction in the treatment of insomnia with liver depression transforming into fire syndrome. </ins><ins>Methods: </ins><ins>A prospective randomized controlled study was conducted. A total of 200 patients with insomnia of liver depression transforming into fire syndrome treated in Nanyang Central Hospital from March 2024 to August 2025 were divided into study group (100 cases) and control group (100 cases) by random number table method. The control group was given oral estazolam tablets, while the study group received orally administered modified Chaihu Jia Longgu Muli Decoction combined with Wendan Decoction based on syndrome differentiation. The treatment course of both groups was 4 weeks. The total effective rate of treatment, traditional Chinese medicine (TCM) syndrome scores, scores of sleep quality and quality of life, laboratory indicators and the incidence of adverse reactions were compared between the two groups. </ins><ins>Results: </ins><ins>The total effective rate of the study group was 92.00%, which was higher than 81.00% of the control group (P＜0.05). After 4 weeks of treatment, the TCM syndrome scores and each item score of Pittsburgh Sleep Quality Index (PSQI) in the study group were lower than those in the control group, while each item score of quality of life was higher (P＜0.05). Compared with the control group, the levels of 5-hydroxytryptamine (5-HT), Brain-Derived Neurotrophic Factor (BDNF) and Norepinephrine (NE) in the study group were higher after treatment (P＜0.05). There was no significant difference in adverse reactions such as dizziness and fatigue, nausea and blurred vision between the two groups (P＞0.05). </ins><ins>Conclusion: </ins><ins>Modified Chaihu Jia Longgu Muli Decoction combined with Wendan Decoction has a remarkable therapeutic effect on patients with insomnia of liver depression transforming into fire syndrome. It can relieve physical and emotional symptoms such as insomnia, irritability and hypochondriac pain, regulate serological indicators, improve sleep and quality of life of patients, with good medication safety, which is worthy of promotion and application.</ins>