Objective To explore the effect of modified Fangfeng Tongsheng powder combined with antihistamine drugs in the treatment of chronic urticaria. Methods A total of 60 patients with chronic urticaria admitted to our hospital from January 2021 to December 2022 were selected as the research objects. They were divided into control group and observation group by random number table method, with 30 patients in each group. The control group was treated with antihistamine drugs, and the observation group was treated with modified Fangfeng Tongsheng powder combined with antihistamines drugs. The clinical efficacy, psychological status, quality of life and adverse reactions were compared between the two groups. Results The total effective rate of the observation group was 96.67%, which was higher than 73.33% of the control group (P <0.05). After intervention, the HAMD and HAMA scores of the observation group were lower than those of the control group (P <0.05). The scores of emotional function, physiological function, social function and health feeling in the observation group were higher than those in the control group (P <0.05). The incidence of adverse reactions in the observation group was 3.33%, which was lower than 23.33% in the control group (P <0.05). Conclusion In the treatment of patients with chronic urticaria, the application of modified Fangfeng Tongsheng powder combined with antihistamine drugs has a definite effect, which can improve the psychological state of patients, improve their quality of life, and reduce the incidence of adverse reactions. It is worthy of clinical application.