Abstract： Objective： To observe the clinical effect of Paidu Xiaozhen Prescription combined with western medicine on malignant tumor with epidermal growth factor receptor inhibitors (EGFRIs)/ programmed cell death-1 (PD-1) associated rash with heat-toxin entering ying syndrome. Methods： A total of 52 cases of patients with malignant tumor with heat-toxin entering ying syndrome who developed rash after receiving EGFRIs / PD-1 treatment were selected and divided into the control group and the treatment group according to the random number table method，with 26 cases in each group. The control group was treated with Desloratadine Citrate Disodium Tablets， and the treatment group was additionally treated with Paidu Xiaozhen Prescription based on the treatment of the control group. Both groups were treated for 14 days. The clinical effects，total symptom scores，severity of rash，and quality of life were compared between the two groups. Results： After 14 days of treatment， the total effective rate was 88.46% in the treatment group， higher than that of 61.54% in the control group (P＜0.05). There were significant differences in the time effect， inter-group effect， and interaction effect of total symptom scores between the two groups (P＜0.05). After 7 days of treatment，the total symptom scores in the two groups were decreased when compared with those before treatment，the total symptom scores in the two groups after 14 days of treatment were decreased when compared with those before treatment and after 7 days of treatment，and the total symptom score in the treatment group was lower than that in the control group during the same period，differences being significant (P＜0.05). After 14 days of treatment， the severity of rash in the two groups were improved when compared with that before treatment，and the improvement of severity of rash in the treatment group was more significant than that in the control group， differences being significant (P＜0.05). After 14 days of treatment， the Dermatology Life Quality Index (DLQI) scores in the two groups were decreased when compared with those before treatment， and the DLQI scores in the treatment group were lower than those in the control group， differences being significant (P＜0.05). Conclusion： Paidu Xiaozhen Prescription combined with western medicine for malignant tumor with EGFRIs/PD-1 associated rash with heat-toxin entering ying syndrome can reduce the severity of rash and improve the quality of life of patients.