Objective To discuss the clinical effect of excimer laser skin therapy instrument combined with traditional Chinese medicine hot compress in the treatment of vitiligo. Methods A total of 250 patients with vitiligo admitted to Nanjing Huaxia Outpatient Department from January 2022 to January 2024 were randomly divided into control group and experimental group, with 125 patients in each group. The control group was treated with 308 nm excimer laser, and the experimental group was treated with 308 nm excimer laser combined with traditional Chinese medicine hot compress. The clinical efficacy, recovery process and adverse reactions of the two groups were compared. Results The total effective rate of treatment in the experimental group (99.20%) was higher than that in the control group (94.40%) (P <0.05). The treatment spot area and repigmentation rate of the experimental group were better than those of the control group (P <0.05). The incidence of adverse reactions in the experimental group (0.80%) was lower than that in the control group (5.60%) (P <0.05). Conclusion 308 nm excimer laser combined with traditional Chinese medicine hot compress is effective and reliable in the treatment of vitiligo, which can accelerate the recovery process and reduce the incidence of adverse reactions.