| Abstract: Objective: To observe the clinical efficacy of TCM syndrome differentiation and treatment combined with external washing of traditional Chinese medicine in the treatment of skin rash associated with EGFR-TKIs. Methods: A total of 63 patients with advanced non-small cell lung cancer (NSCLC) who developed skin rash related to EGFR-TKI were randomly divided into the treatment group (n = 32) and the control group (n = 31). According to the different stages and manifestations of skin rash development, the treatment group was divided into wind-heat type (initial stage), damp-heat type (middle stage) and yin-deficiency type (late stage). Xiaofengsan, Bixingyishen Decoction and Shashen Ophiopogon Decoction were given orally 1 dosage per day, and Chinese medicine was given external washing 2 times per day;The control group was given erythromycin ointment for external use twice a day and minocycline 100 mg twice a day with infection;The course of treatment was 6 weeks.Before and after treatment, the grade of skin rash and the changes of clinical symptoms of traditional Chinese medicine were observed. Results: In TCM treatment group, 25 cases were effective, 4 cases stable, 3 cases ineffective, the effective rate was 78.13%;In the control group, 7 cases were effective, 11 cases were stable, 13 cases were ineffective, and the effective rate was 22.6%. Compared with the control group, the TCM treatment group was significantly improved in skin rash related to EGFR-TKIs (P < 0.05). The TCM symptom score of lung cancer before treatment in the TCM treatment group and the control group was 35.38 ± 3.69 and 34.38 ± 4.21, respectively, with no significant difference (P > 0.05);The symptom score of TCM group was 29.59 ± 3.06 after treatment, which was significantly different from that before treatment (P < 0.05). In the control group, the scores of TCM symptoms after treatment were not significantly different from those before treatment (P > 0.05);After treatment, the TCM symptom score of the treatment group and the control group was 33.29 ± 4.08, there was significant difference (P < 0.05). Conclusion: TCM staged treatment combined with external washing can significantly improve the treatment of advanced non-small cell lung cancer patients with EGFR-TKIs related rash, improve the clinical symptoms of patients with TCM.