To explore the therapeutic effect of Binghuangfule ointment combined with desonide cream on nodular prurigo. Methods A total of 70 patients with nodular prurigo admitted to Lingyun Street Community Health Service Center of Xuhui District from April 2021 to June 2023 were selected as the research objects. According to different medication regimens, they were divided into control group and study group, with 35 patients in each group. The control group was treated with desonide cream, and the study group was treated with Binghuangfule ointment combined with desonide cream. The clinical efficacy, clinical symptom score, quality of life and adverse reactions were compared between the two groups. Results The total effective rate of treatment in the study group was 94.29%, which was higher than 77.14% in the control group (P <0.05). The scores of erythema, papules, skin lesions and pruritus in the study group were lower than those in the control group (P <0.05). After treatment, the scores of DLQI in the study group were lower than those in the control group (P <0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P >0.05). Conclusion Binghuangfule ointment combined with desonide cream is effective in the treatment of nodular prurigo, which can effectively reduce the clinical symptoms of patients, and will not increase the incidence of adverse reactions. Meanwhile, it has positive significance for improving the quality of life of patients.