OBJECTIVE： To observe the clinical efficacy and safety of Xiaozhen zhiyang spray in the treatment of EGFRI-associated rash. METHODS： A total of 60 malignant tumor patients suffering from rash induced by EGFRI were divided into trial group （40 cases） and control group （20 cases） according to the patient’s willingness. Control group didn’t received any therapy for rash. Trial group received Xiaozhen zhiyang spray for several times a day according to the degree of rash as 1-2 times/d for first degree， 2-3 times/d for second degree， 3-5 times/d for third degree， and the treatment course lasted for 2 weeks. Rash degree and improvement， itching degree and improvement， daily life quality index （DLQI） score before and after treatment as well as the occurrence of ADR were compared between 2 groups. RESULTS： before treatment， there was no statistical significance in rash and itching degree， or DLQI score between 2 groups （P＞0.05）. After treatment， rash and itching degree of trial group were improved significantly compared to before treatment and control group， with statistical significance （P＜0.05）. The total response rates of rash and itching therapy in trial group were significantly higher than control group （67.50％ vs. 20.00％， 70.00％ vs. 15.00％）， with statistical significance （P＜0.05）. DLQI score of trial group was significantly lower than before treatment and control group， with statistical significance （P＜0.05）. There was no statistical significance in DLQI score of control group before and after treatment （P＞0.05）. No obvious ADR was found in trial group. CONCLUSIONS： Xiaozhen zhiyang spray can effectively relieve EGFRI-associated rash and itching as well as improve the quality of life for patients.